2-Substituted-3,4-epoxycyclopentan-1-ones, and 2-substituted-3,4-epoxycyclopentan-1-ols

ABSTRACT

This disclosure describes 2-substituted-3,4-epoxy-cyclopentan-1-ones, 2-substituted-3,4-epoxycyclopentan-1-ols, and various 2-substituted-cyclopentenones useful as intermediates for the preparation of certain 11-hydroxy- and 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives which possess bronchodilator, hypotensive, and anti-ulcer activity.

This is a division of application Ser. No. 355,101, filed Apr. 27, 1973and now abandoned.

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel hydroxy substituted prostanoic acids andderivatives as well as to intermediates and methods for theirpreparation. These methods embrace novel and useful procedures for thepreparation of prostaglandin E₁, 11-deoxyprostaglandin E₁,13-dihydroxyprostaglandin E₁, and other known biologically importantprostaglandin congeners. The novel compounds of this invention may berepresented by the following general formula: ##EQU1## wherein n is aninteger having the value 1 or 2; R₁ is hydrogen, lower alkoxy,triphenylmethyl, or triphenylmethyl in which one or two of the phenylrings is substituted with an alkyl or an alkoxy group having up to 3carbon atoms; R₂ is a straight chain alkyl group having from 2 to 10carbon atoms, a straight chain alkyl group having from 2 to 10 carbonatoms and substituted with one or two alkyl groups each having from oneto three carbon atoms, a straight chain alkenyl group having from 3 to10 carbon atoms, a straight chain alkenyl group having from 3 to 10carbon atoms and substituted with one or two alkyl groups having betweenthem from 2 to 5 carbon atoms, or a straight chain alkenyl group havingfrom 3 to 10 carbon atoms; R₃ is hydroxy or an alkoxy group having from1 to 12 carbon atoms; Y is a divalent radical selected from the groupconsisting of those of the formulae: ##EQU2## Z is a divalent radicalselected from the group consisting of those of the formulae:

    --(CH.sub.2).sub.m --, ##EQU3##

    --(CH.sub.2).sub.m --O--CH.sub.2 --, --(CH.sub.2).sub.m --S--CH.sub.2 --, or ##EQU4## WHEREIN M IS AN INTEGER FROM 3 TO 8, INCLUSIVE, P IS AN INTEGER FROM 2 TO 6 INCLUSIVE, R.sub.4 is an alkyl group having up to 3 carbon atoms, and R.sub.5 is an alkyl group having up to 3 carbon atoms, a fluorine atom, or a phenyl group; R.sub.6 is hydrogen or an alkyl group having up to three carbon atoms; R.sub.7 is hydrogen or an alkyl group having up to 3 carbon atoms; and the moiety --C.sub.13 --C.sub.14 -- is ethylene, trans-vinylene, or cis-vinylene; with the first proviso tht when n is 1, R.sub.1 is hydrogen, R.sub.7 is hydrogen, Z is --(CH.sub.2).sub.m -- and --C.sub.13 --C.sub.14 -- is ethylene or trans-vinylene then R.sub.2 does not include a straight chain alkyl group having from 2 to 10 carbon atoms; and with the second proviso that when Z is ##EQU5## R.sub.1 is hydrogen, R.sub.2 is a straight chain alkyl group having from 2 to 10 carbon atoms and R.sub.7 is hydroen then --C.sub.13 --C.sub.14 -- is ethylene or cis-vinylene; and with the third proviso that when R.sub.6 is alkyl then R.sub.1 is hydrogen; and with the fourth proviso that only one unsaturated bond can be directly adjacent to C.sub.15 ; and with the fifth proviso that when R.sub.7 is an alkyl grop then the groups attached to the C.sub.8 position may have the 8α-alkyl(8-iso) configuraton of the formula: ##EQU6##

Embraced within the scope of the present invention are all the possibleoptical isomers of the above general formula. Also embraced within thescope of the present invention are the non-toxic, pharmaceuticallyacceptable salts of the novel compounds of the present invention when R₃is hydroxy. The cations comprised in these salts include, for example,the non-toxic metal cations such as the sodium ion, potassium ion,calcium ion, and magnesium ion as well as the organic amine cations suchas the tri(lower alkyl)amine cations (e.g., triethylamine,triethanolamine) procaine, and the like.

The novel compounds of the present invention are usually obtainable asoils having characteristic absorption spectra. They are relativelyinsoluble in water but are relatively soluble in common organic solventssuch as ethanol, ethyl acetate, dimethylformamide, and the like. Thecationic salts of the compounds when R₃ is hydroxy are, in general,while to yellow crystalline solids having characteristic melting pointsand absorption spectra. They are relatively soluble in water, methanol,and ethanol but are relatively insoluble in benzene, diethyl ether, andpetroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which havebeen obtained from various animal tissues, and which stimulate smoothmuscle, lower arterial blood pressure, antagonize epinephrine-inducedmobilization of free fatty acids, and have other pharmacological andautopharmacologicl effects in mammmals. See Bergstrom et al., J. Biol.Chem. 238, 3555 (1963) and Horton, Experientia 21, 113 (1965) andreferences cited therein. All of the so called natural prostaglandinsare derivatives of prostanoic acid: ##EQU7## The hydrogen atoms attachedto C-8 and C-12 are in trans-configuration. When the two side-chains (orthe C-8 and C-12 hydrogens) are cis to each other, the compounds arereferred to as 8-iso prostaglandins. The natural prostaglandinsrepresent only one of the possible optical isomers. The compounds ofthis invention include all possible optical isomers.

The novel compounds of the present invention may be readily preparedfrom certain cycloalkenone intermediates which may be represented by thefollowing general formula: ##SPC1##

wherein R'₃ is an alkoxy group having from 1 to 12 carbon atoms; and nand Z are as hereinabove defined.

The cycloalkenone intermedites may be readily prepared from2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone in accordancewith the reaction schemes set forth in Flowsheets A, B, C, I and J.##SPC2##

wherein m and n are as herein above defined and X is iodo or bromo. Inaccordance with this reaction scheme, the cycloalk-2-en-1-ones (VIII)are developed by firsst converting 2-carbethoxycyclopentanone or2-carbethoxycyclohexanone (I) to the sodium enolates thereof by means ofsodium hydride in dimethoxyethane and then treating the sodium enolatewith an ethyl ω-haloalkanoate (II). There is thus obtained thecorresponding 2-carbethoxy-2-(ω-carbethoxyalkyl)cycloalkanone (III)which is then hydrolyzed and decarboxylated to afford the2-(ω-carboxyalkyl)cycloalkanone (IV). This acid is then esterified withethanol whereby the 2-(ω-carbethoxyalkyl)cycloalkanone (V) is obtained.The reaction conditions for carrying out the above sequence of reactionsare well known in the art. The conversion of the cycloalkanone (V) tothe enol acetate (VI) is effected by heating with acidic anhydride inthe presence of p-toluenesulfonic acid. Preparation of the enol acetate(VI) usually requires heating for a period of from about eight tothirty-six hours. During this period, it is preferable to allowby-product acetic acid to distill out in order to force the rection tocompletion. The bromination of the enol acetates (VI) to the2-bromocycloalkanones (VII) is preferably carried out in a two phasesystem as follows. A solution of bromine in chloroform is added to arapidly stirred mixture of a solution of the enol acetate (VI) inchloroform and an aqueous solution of an acid acceptor such as calciumcarbonate or soda ash. This addition is carried out at 0°-5° C. over aperiod of about half an hour, stirring is continued for an additionalperiod of about half an hour to a few hours, and te product (VII) isthen isolated by standard procedures. The dehydrobromination of the2-bromocycloalkanones (VII) is preferably carried out indimethylformamide with a mixture of lithium bromide and lithiumcarbonate at the reflux temperature for a period of about 30 minutes toan hour or so. The so formed cycloalk-2-em-1-ones (VIII) are alsoisolated by standard procedures well known in the art. Substitution ofX-(CH₂)_(m) --C(R₄)₂ --CH₂ --CO₂ C₂ H₅ for (II) in Flowsheet A andcarrying through the sequence of transformations illustrated therein isproductive of the following cycloalk-2-en -1-one VIIIa): ##EQU8##wherein X, n, m and R₄ are as hereinabove defined.

The required cycloalk-2-en-1-one intermediates of general structure(XVI), wherein the side-chain has a lower alkyl group, fluorine atom orphenyl group alpha to the carbethoxy function, may be prepared inaccordance with the following reaction scheme: ##SPC3##

wherein n, m and R₅ are as hereinabove defined and G is a lower alkyl oraryl group. In accordance with this reaction scheme, the2-(ω-carbethoxyalkyl)cycloalk-2-en-1-ones (IX) are converted to thecorresponding 1-methoximino-2-(ω-carbethoxyalkyl)-2-cycloalkenes (X) bytreatment with methoxyamine. With the ring carbonyl function thusblocked it is possible to effect a preferential reduction of the estergroup by treatment with diisobutylaluminum hydride. The resultingalcohol (XI) is converted to a tosylate derivative (XII), whichundergoes displacement on treatment with the sodium salt of a diethyl R₅-substituted malonate (XIII) to provide the disubstituted malonatederivaties (XIV). Hydrolysis and decarboxylation as well as concomittantcleavage of the methoximino blocking group provides the desired(2-(ω-carboxy-ω-R₅ -substituted-alkyl)cycloalk-2-en-1-ones (XV), whichare readily converted to the corresponding ester (XI) by the usualprocedure via the acid chloride and subsequent treatment with theappropriate alcohol in the presence of a tertiary amine.

The requisite 2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-ones (XXII)and 2-(ω-carbethoxy-ω-1-thia-alkyl)-cycloalk-2-en-1-ones (XXVI) may beprepared in accordance with the reaction schemes of Flowsheet C, whereinn and m are as hereinbefore defined. ##SPC4##

In accordance with the reaction scheme shown in Flowsheet C, for thepreparation of the oxa derivative (XXII), an appropriate2-(ω-carbethoxyalkyl)cycloalk-2-en-1-one (XVII) is converted to thecorresponding methoxime (XVIII), the ester function of which is thenpreferentially reduced with diisobutylaluminum hydride to afford themethoxime alcohol (XIX). The alcohol (XIX) is converted on treatmentwith n-butyl lithium to the lithio alcoholate, which then is O-alkylatedby reaction with ethyl bromoacetate to provide (XX). Hydrolysis withacetone-aqueous hydrochoric acid furnishes the deblocked keto-acid(XXI), which is then re-esterified with ethanol in the presence ofp-toluenesulfonic acid to give the required2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-one (XXII). O-Alkylationcan also be accomplished by treatment of the lithio alcoholate of (XIX)with sodium or other metal salt of bromoacetic acid, in which case thefree carboxylic acid corresponding to ester (XX) is obtained. Hydrolysisas for (XX) provides the keto acid (XXI).

The preparation of the thia derivative (XXVI), proceeds from theintermediate alcohol (XIX), which after conversion to the tosylateintermedite (XXIII) and reaction with the sodium salt of ethylmercaptoacetate furnishes intermediate (XXIV). Deblocking of XXIV withacetone-aqueous hydrochloric acid provides the keto-acid (XXV), which onre-esterification with ethanol gives the required2-(ωcarbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI).

Certain of the 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivativesof this invention, as defined in the general formula on page 1 above,may be prepared from cycloalkenone (XXXI) and the triphenylmethoxysubstituted 1-alkyne (XXVII) as depicted in Flowhseet D. In Flowsheet D,n, R₃, R'₃ and Z are as hereinabove defined; R'₂ is a straight chainalkyl group having from 2 to 10 carbon atoms, a straight chain alkylgroup having from 2 to 10 carbon atoms and substituted with one or twoalkyl groups each having from one to three carbon atoms, a straightchain alkenyl methyl group having from two to nine carbon atoms, or astraight chain alkenyl methyl group having from two to nine carbon atomsand substituted with one or two alkyl groups having between them 2 to 5carbon atoms; and R is a lower alkyl group. ##SPC5##

In accordance with the reaction scheme of Flowsheet D, thetriphenylmethoxy substituted 1-alkyne (XXVII) is treated withdiisobutylaluminum hydride (XXVIII). This reaction of the 1-alkyne(XXVII) with diisobutylaluminum hydride (XXVIII) provides the alane(XXIX) containing the trans-double bond and is carried out in an inertsolvent such as benzene, toluene, and the like at temperatures in therange of 40°-60°C. for several hours. It can also be carried out in asolvent such as tetrahydrofuran, usually in an approximate 2:1 mixturewith benzene or hexane; in which case the reaction requires somewhatmore vigorous conditions, usually treating at about 70°-75°C. for abouteighteen hours. The subsequent reaction with methyl or n-butyl lithium(R-Li) is preferably carried out in a mixture of the above solvents withan ether-type solvent such as diethyl ether, dibutyl ether,tetrahydrofuran and the like. This reaction is rapid and is preferablycarried out at 0°-10°C. with cooling. The conjugate 1,4-addition of themelting alanate salt (XXX) to the cycloalk-2-en-1-one (XXXI) ispreferably carried out at ambient temperatures for a period of 12 to 24hours. This reaction is also best carried out in an ether-type solventsuch as diethyl ether, dibutyl ether, tetrahydrofuran, and the like. Theintermediate alanate-enolate adduct is then carefully hydrolyzed in situwith dilute hydrochloric acid with cooling, and the products (XXXII) areisolated in the usual manner well known in the art. Removal of thetriphenylmethyl blocking group can then be accomplished by treating withweak acid. A preferred procedure involves heating at 45°C. for 3.5 hoursin a solvent system consisting of acetic acid:tetrahydrofuran:water inthe proportion of 4:2:1. Saponification in the usual manner of theresulting alkyl ester (XXXIII, R₃ =alkoxy) provides the correspondingcarboxylic acid (XXXIII, R₃ =OH).

All available evidence leads us to the conclusion that in the product(XXXIII) the two side-chains attached to C₈ and C₁₂ are trans to eachother. However, we are not certain of the configurational relationshipin product (XXXII) as it is obtained directly from the alanate process.These products may have the side-chains in a trans or cis relationshipor they may be a mixture containing both the trans- and cis-isomers.This is indicated in the nomenclature of the compounds involved by thedesignation of 8ξ. In order to ensure a trans-relationship in both(XXXII) and (XXXIII) these products can be submitted to conditions knownin the literature to equilibrate the cis-8-iso-PGE₁ to a mixturecontaining about 90% of the trans product. These conditions involvetreatment with potassium acetate in aqueous methanol for 96 hours atroom temperature.

The triphenylmethyl blocking group for the hydroxy function in (XXVII)etc. is an important feature of this process and other oxygen blockinggroups, e.g., tetrahydropyranyl and alkyl, are not compatible with aclean cis-addition of diisobutyl aluminum hydride (XXVIII) to the alkyne(XXVII) to provide the desired trans-vinyl function. Alternativeprocedures for the preparation of novel lithio alanate reagents usefulfor the introduction of the Δ¹³ -trans 15-oxy β-chain by conjugate1,4-addition are illustrated in Flowsheet K further below.

The intermediates for the introduction of the Δ¹³ -15 -hydroxyside-chain are an integral part of this invention and they may berepresented by the following general formulae (A), (B), (C), (D) and (E)wherein R'₂ is as hereinabove defined, R is a lower alkyl group, notnecessarily the same for each use, and R' is an alkyl group having fromone to ten carbon atoms not necessarily the same for each use, W₁ islower alkoxy, triphenylmethyl, or a triphenylmethyl group in which oneor two of the phenyl rings is substituted with a lower alkoxy group; W₂is lower alkoxy, triphenylmethyl, a triphenylmethyl group in which oneor two of the phenyl rings is substituted with a lower alkoxy group,tetrahydropyranyl, α-(lower alkoxy) substituted lower alkyl, t-butyl, ora tri(lower alkyl)silyl group; X₁ is iodo or bromo; s is an integerhaving the value of one to three inclusive, and t is an integer havingthe value of one to three inclusive, with the proviso that the sum of sand t must be equal to four. ##EQU9##

The alanate conjugate addition procedure is also useful for thesynthesis of prostaglandin E₁ (XL) as illustrated in Flowsheet E. Thisreaction sequence is carried out in the same manner as described for thesequence in Flowsheet D. It is to be noted that the introduction of theΔ¹³ -15-oxy chain proceeds trans to the 11-oxy function. For thissynthesis, it is best to use the tetrahydropyranyl or trialkylsilylesters, since these esters can be hydrolyzed under conditions compatiblewith the stability of the β-ketol feature of prostaglandin E₁. Alkylesters would be hydrolyzed by fermentation with Baker's Yeast. Thetetrahydropyranyl or trialkylsilyl, and triphenylmethoxy blocking groupsare removed by mild acid treatment, for example with aceticacid:tetrahydrofuran:water (4:2:1) as described hereinabove. Applicationof the lithio alanate conjugate addition process to the synthesis ofprostglandins E₂ and E₃ is described below in connection with FlowsheetN. ##SPC6##

The 13-dihydro derivatives (C₁₃ -C₁₄ is ethylene) of this invention canbe prepared by reduction of the Δ¹³ function in the corresponding13-prostenoic acids or esters. This reduction can be accomplished byhydrogenation. However this procedure is not cleanly applicable in thepresence of other double bonds in the molecule. In the latter instancethe 13-dihydro derivatives are preparable via conjugate addition of aGrignard derivative (XLII) to cycloalkenone (XLI) in the presence of acatalyst such as the tributylphosphine cuprous iodide complex as setforth in Flowsheet F, wherein n Z, R₂ and R'₃ are as hereinabovedefined; Q is a blocking group; and X is chlorine, bromine or iodine,preferably bromine or iodine. The blocking group (Q) for the hydroxylfunction in (XLII) can be any group stable to the Grignard reagent andwhich can later be removed by chemical treatment (e.g., mild hydrolysisor catalytic hydrogenolysis in the absence of carbon to carbon doublebonds elsewhere in the molecule) to which the remainder of the moleculeis stable. Suitable blocking groups, therefore, may be, for example,benzyl, diphenylmethyl, triphenylmethyl, tetrahydropyranyl, or a moietyof the formula ##EQU10## wherein R₁₁ is hydrogen, methyl or ethyl. Amongthe above-described blocking groups, we have found tert-butyl to beparticularly convenient and useful. ##SPC7##

In accordance with the above reaction scheme, the conjugate 1,4-additionof a 3-(substituted hydroxy)alkyl or alkenyl magnesiium halide (XLII) toa cycloalk-2-en-1-one (XLI) is carried out in the presence of acatalyst. In general, Grignard reactions with conjugated ketones provide1,2-addition products; conjugate 1,4-addition is usually accomplishedwhen the reaction is carried out in the presence of a cuprous chlorideor cuprous acetate catalyst. It is therefore most unexpected that thereaction of the cycloalkenone (XLI) with a Grignard reagent (XLII) inthe presence of either of the aforementioned catalysts does not giveappreciable amounts of the desired 1,4-conjugte addition products. Thenovel feature of our process is provided by the use, as a catalyst, of acuprous halide complex with a trisubstituted phosphine, a trialkylphosphonate, a tertiary amine or a heterocycle containing a basicnitrogen (e.g., pyridine). We have found it preferable to usetributylphosphine-cuprous iodide complex; (C₄ H₉)₃ P.CuI. The reactionis best carried out in the usual way in an ether-type solvent such asdiethyl ether, dibutyl ether, tetrahydrofuran, and the like, at roomtemperature for a period of time of from two to eighteen hours. Theintermediate magnesium halide-enolate adduct is then hydrolyzed in situ,preferably with ammonium chloride, at room temperature and the product(XLIII) is isolated in the usual manner well known in the art.

When the blocking group is a tertiary alkyl moiety such as tert-butyl,deblocking of (XLIII) to afford (XLIV) is conveniently effected bytreatment with glacial trifluoroacetic acid at from -5°C. to 10°C. for aperiod of one to three hours. Since this procedure may lead to partialtrifluoroacetylation of the free hydroxy function, it is preferablyfollowed by treatment with aqueous ammonia (about 1.0N concentration)for about 15 minutes at ambient tempertures. When the blocking group istetrahydropyranyl, its removal is readily effected with dilute acid.When the blocking group is a moiety such as benzyl, diphenylmethyl ortriphenylmethyl, deblocking of (XLIII) is conveniently effected bycatalytic hydrogenolysis, procedures for which are well known in theart. In the instance of triphenylmethyl, deblocking is preferablyeffected by treating with acetic acid-tetrahydrofuran:water (4:2:1) atabout 45°C. for about 3.5 hours.

Mild acid treatment results in hydrolysis of the tetrahydropyranylesters; alkyl esters can be hydrolyzed by the usual saponificationtechniques.

When the cycloalkanone esters (XLIII) are formed by quenching of thereaction mixture with aqueous ammonium chloride solution, the relativestereochemical relationship of the two side-chains is not known withcertainty. Therefore, the bond linking the Grignard-derived side-chainto the cycloalkyl ring is indicated by a ˜ bond in (XLIII). However, inany case, the subsequent deblocking and ester hydrolysis proceduresensure the development, at least in predominant proportion, of thethermodynamically favored trans-relationship between the twoside-chains, as is depicted in structure (XLIV) of the reaction scheme.

An alternative method for the introduction of the Δ¹³ -15-hydroxyside-chain involves 1,4-conjugate addition to cycloalkenone (LV) of avinyl Grignard reagent [(LIII) + (LIV)] in the presence of a catalystsuch as the tributylphosphine cuprous iodide complex followed bydeblocking. From this process, in addition to the product (LVIII)containing the C₁₃ -C₁₄ moiety as a trans-vinylene function there alsois obtained the corresponding product (LIX) in which the C₁₃ -C₁₄ moietyis a cis-vinylene function. These novel cis-Δ¹³ derivatives are alsoembraced within the scope of this invention. The reaction sequence forthe "vinyl" Grignard process is illustrated in flowsheet G, whichfollows, and in which W₂, n, Z, R₃ and R'₃ are as hereinabove defined,and R"₂ is a straight chain alkyl group having from 2 to 10 carbonatoms, or a straight chain alkyl group having from 2 to 10 carbon atomsand substituted with one or two alkyl groups having from one to threecarbon atoms. ##SPC8##

In accord with the reaction sequence of Flowsheet G the vinyl Grignardreagent (LIII + LIV), is prepared under an inert atmosphere in arelatively limited amount of anhydrous tetrahydrofuran. More vigorousconditions (e.g., heating in an oil bath at 70°-80°C., one hour), forthe formation of the Grignard reagent (LIII + LIV) favors the proportionof Δ¹³ -cis isomer (LIX) in the product of conjugate addition. Milderconditions (for example 35°-47°C., 1 hour) favors the proportion of Δ¹³-trans isomer (LVIII) in the final product.

Conjugate addition of the vinyl Grignard reagent mixture [(LIII) +(LIV)] to cycloalkenone (LV) is then preferably carried out by additionof the Grignard to the cycloalkenone dissolved in an ether type solvent,e.g., diethylether, containing a catalyst such as thetributylphosphine-cuprous iodide complex at a temperature of about 0°C.After a period of about thirty minutes to three hours the reactionmixture is poured onto aqueous concentrated ammonium chloride solutionto give (LVI) + (LVII). As explained hereinabove, at this stage therelationship of the two side-chains to each other is not determined. Inany event, deblocking the 15-hydroxy function with weak acid (whichprocedure also hydrolyzes trialkysilyl or tetrahydropyranyl esters)provides the product (LVIII) and (LIX) in which the chains are trans toeach other. In the instance of alkyl esters, saponification provides thecorresponding carboxylic acids. The Δ¹³ -cis and Δ¹³ -trans isomers canbe separated from each other by the usual techniques of chromatography;particularly useful in liquid-liquid partition chromatography.

The precursor 3-hydroxy-1-trans-alkenyl bromides (LI) can be prepared,as illustrated in Flowsheet G, by condensation of acetylene (XLV) withan acid chloride (XLVI) in the presence of aluminum trichloride. Theresulting 3-oxo-1-chloro-trans-1-alkylene (XLVII) is then converted tothe corresponding 1-bromo derivative (XLVIII), by reaction with excesslithium bromide. This reaction is preferably carried out in ketonesolvents, such as 2-pentanone or acetone. Reduction of the 3-ketofunction in (XLVIII), with for example, sodium borohydride provides thealcohol (LI). The alcohol function is then blocked to give (LII).Alternatively, the 3-oxo vinyl bromide (XLVIII) can be prepared directlyfrom the acyl bromide (L) and acetylene (XLIX) in the presence ofaluminum tribromide, preferably in ethylene dibromide.

The "vinyl Grignard" procedure outlined in Flowsheet G represents anovel, useful and convenient procedure for the synthesis of13-prostenoic acids and the novel Grignard reagents represented byformulae (LIII) and (LIV) are to be considered as embraced within thescope of this invention.

The vinyl Grignard technique can also be applied to a useful synthesisof prostaglandin E₁ and the novel Δ¹³ -cis-prostaglandin-E₁ asillustrated in Flowsheet H, below. Thus, treatment of cyclopentanone(LX) with Grignard [(LXI + (LXII)] in accordance with the considerationsdiscussed hereinabove, provides the conjugate addition products (LXIII)plus (LXIV), mild acid hydrolysis of which furnishes prostaglandin E₁(LVX) and Δ¹³ -cis prostaglandin E₁ (LXVI), separable by chromatography.##SPC9##

The preparation of the cycloalkenone intermediates (LXXVI, LXXVII)bearing a cis double bond in the carboxylic acid side chain can beaccomplished by the sequence illustrated in Flowsheet I, which followsand in which n and p are as hereinabove defined. ##SPC10##

In the above Flowsheet I, the sequence wherein a2-carbalkoxycycloalkanone (LXVII) is transformed to a2-(β-hydroxyethyl)cycloalk-2-en-1-one (LXXIII) is carried out in themanner described in Flowsheet A. Methyl ether cleavage of thecorresponding 2-(β-methoxymethyl)cycloalkenone is achieved by treatingwith boron tribromide. Oxidation of the alcohol (LXXIII) with Collinsreagent [chromium trioxide-pyridine complex in methylene chloride underanhydrous conditions; J. C. Collins, W. W. Hess, and F. J. Frank,Tetrahedron Letters, 3363 (1968)] provides the aldehyde (LXXIV), whichis then treated in anhydrous dimethylsulfoxide with the ylid (LXXV)prepared from an (ω-carboxyalkyl)triphenyl phosphonium bromide andsodium hydride. The use of dimethylsulfoxide as a solvent for thisreaction leads to the predominant formation of the desired cis doublebond derivative (LXXVI). The acid function in (LXXVI) can be esterifiedin the usual fashion; with diazomethane, the methyl ester (LXXVII) isobtained.

Cyclopentenones such as (LXXVI wherein n=1) may also be prepared by thesequence illustrated in Flowsheet J, which follows and in which p is ashereinabove defined. ##SPC11##

In Flowsheet J above the bicyclic hemiacetal (LXXVIII) [P. A. Grieco,Journ. Org. Chem., 37, 2363 (1972)] is treated with ylid (LXXIX) to givethe 1-hydroxy-3-cyclopentene (LXXX). Oxidation with Jones reagent givesthe corresponding ketone (LXXXI), which on base treatment furnishes therequired cyclopentenone (LXXXII), which can then be esterified in theusual manner.

Certain of the intermediates illustrated in Flowsheets I and J, inparticular the compounds of formulae (LXXI), (LXXII), (LXXIII), (LXXIV),(LXXVI) (LXXVII) (and related esters), (LXXX) and (LXXXI) are novel anduseful compounds and are embraced within the scope of this invention.

Alternative procedures for the preparation of the alanate intermediatesto that discussed in connection with Flowsheet D above are illustratedbelow in Flowsheet K, wherein R', R'₂, R"₂ and W₂ are as hereinabovedefined. ##EQU11##

In accordance with the sequence of Flowsheet K above the1-iodo-trans-1-alkenyl-3-oxo derivative (LXXXIV) is prepared by iodideinterchange, preferably in acetone or similar ketone, from thecorresponding chloride (LXXXIII), the preparation of which is describedin connection with Flowsheet G above. Reduction of (LXXXIV) to thealcohol (LXXXVI) can be accomplished in the usual manner with sodiumborohydride. The hydroxy function is then blocked to give (LXXXV, R'₂-R"₂). Treatment of the acetylene, ##EQU12##a with one equivalent ofdisiamylborane (prepared in situ from diborane and 2-methyl-2-butene)and then with excess anhydrous trimethylamine oxide followed bytreatment with an aqueous solution of excess sodium hydroxide and atetrahydrofuran solution of excess iodine is also productive of (LXXXV).Treatment of the trans-1-alkenyl iodide (LXXXV) at low temperatures,preferably at about -30°C. to -78°C., in an inert solvent, e.g., hexaneor toluene, with an alkyl lithium, e.g., butyl lithium, provides thetrans-1-alkenyl lithium reagent (LXXXVII). Treatment of this lithioderivative with a tri-alkyl aluminum furnishes the trans-1-alkenyltrialkyl alanate (LXXXVIII). Treatment of a dialkyl aluminum chloridewith two molar equivalents of lithio reagent (LXXXVII) gives thebis(trans-1-alkenyl)dialkyl alanate (LXXXIX) and treatment of analkylaluminum dichloride with three molar equivalents of lithio reagent(LXXXVII) affords the tris(trans-1-alkenyl)alkyl alanate (XC).

Each of the three types of alanates, (LXXXVIII), (LXXXIX) and (XC), canbe utilized for 1,4-conjugate addition reactions as describedhereinabove in connection with Flowsheets D and E above. Thus,substitution of (LXXXVIII), (LXXXIX) or (XC) for alanate (XXX) inFlowsheet D will provide the indicated products of the Flowsheet.Similarly, substitution of (LXXXVIII), (LXXXIX) or (XC) in which R'₂ isn-pentyl for alanate (XXXVII) in Flowsheet E provides prostaglandins E₁.In general the mono alkenyl alanate (LXXXVIII) is preferred because itis more economical in the use of vinyl halide.

With regard to the cycloalkenones of Flowsheets D, E, F, G and H itshould be noted that the blocking groups for the 4-hydroxy function aswell as for the carboxylic acid may also be a tri-alkylsilyl group,e.g., trimethylsilyl, dimethyl-t-butylsilyl or dimethylisopropylsilyl.Cyclopentanones blocked in this manner are illustrated below in formula(XCI) and (XCII) wherein m, n, Z and R' (not necessarily the same foreach use) are as hereinabove defined. ##EQU13##

All the novel products of this invention exclusive of certainintermediates bear a hydroxy or oxy function substituted at or at whatultimately becomes the C₁₅ atom of the product prostanoic acids andesters. Thus in at least most instances a 15-"normal" and a 15-"epi"racemate is obtained in at least near equal proportions. Each of theracemates contains equal amounts of the enantiomer wherein C₁₅ is in theS configuration and the enantiomer wherein it is in the R configuration.The racemates are separable from each other by the usual techniques ofchromatography. Also, resolution in the usual way of the β-chainprecursor [for example, the resolution of 3-hydroxy-1-octyne isdescribed in the literature] see R. Pappo, P. Collins and C. Jung. Ann.N.Y. Acad. of Science, 180 (Prostaglandins), 64(1971); J. Fried et al.,ibid, p. 381. Resolution prior to the conjugate addition operation willprovide the diastereomers wherein the C₁₅ atom is either in the 15(S) or15(R) configuration, as desired. Separation of the diastereomers soobtained, for example, by chromatography, will give the fully resolved(d and l) products provided there are no asymmetric carbon atoms otherthan at C₈ and C₁₂. The presence of other asymmetric sites requiresadditional resolution steps in order to obtain a single atipode. Thecompounds of this invention embrace all possible optical isomers.

The 11-deoxy-9-keto derivatives (XCIV) of this invention can beconverted to the corresponding 9-hydroxy derivatives. If this conversionis effected with sodium borohydride, the product is a mixture of 9α- and9β-hydroxy derivatives (XCIII) and (XCV) as set forth in the followingreaction scheme: ##SPC12##

wherein R₂, R₃, R₆, R₇, Z, n and --C₁₃ -C₁₄ -- are as hereinabovedefined. In general, when the reaction is carried out with lithiumperhydro-9β-boraphenalyl hydride [H. C. Brown and W. C. Dickason, Journ.Amer. Chem. Soc., 92, 709 (1970)] the product is at least predominantlythe 9α-hydroxy derivative (XCIII), wherein the 9-hydroxy group is cis tothe side-chain attached to C₈.

In accordance with accepted convention, an α-substituent at the 8-, 9-,or 12-positions is behind the plane of the paper whereas a β-substituentat these positions is in front of the plane of the paper. This isusually represented by a - - - bond for an α-substituent, a -- bond fora β-substituent, and a bond where both are indicated. Thus, the9-hydroxy derivatives may be variously represented as follows: ##EQU14##

A useful procedure for the introduction of the 15-lower alkyl group (R₆)is illustrated by the sequences of Flowsheet M, which follows. ##SPC13##

In Flowsheet M above n, Z, R₂, R₇ and R₆ are as hereinabove defined. Inthe sequence depicted in Flowsheet M the 9,15-diol (XCVI) is treatedwith 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (XCVII), whichpreferentially oxidizes the allylic alcohol function at C₁₅ to give the15-ketone (XCVIII). Blocking of the remaining hydroxy function as atrimethylsilyl ether gives (IC) which is reacted with the alkylGrignard, R₆ MgI, to give the 15-alkyl-15-hydroxy derivative (CI).Hydrolysis of the silyl ether blocking group then gives the diol ester(C), saponification of which gives (CII). Oxidation of the secondary9-hydroxy function in (C) provides the 15-alkyl-9-oxo ester (CIII),saponification of which furnishes (CIV). (A similar sequence can beeffected with the Δ¹³ -cis-series.)

The processes of this invention are also useful for the preparation ofprostaglandin E₂ and prostaglandin E₃ and thus also PGF₂.sub.α andPGF₃.sub.α by reduction, for example with lithiumperhydro-9β-boraphenalyl hydride. The 4-hydroxycyclopentenoneintermediate (CXI) required for these syntheses is prepared inaccordance with the procedure illustrated in Flowsheet N which followsand in which is also shown the transformation of this compound toprostaglandins E₂ and E₃. In Flowsheet N, J is an appropriate blockinggroup for the hydroxy and ester function in (CXI) which is compatiblewith the conjugate addition reaction and also is ultimately removable byacid-catalyzed hydrolysis or other techniques which will not disrupt thesensitive 11-oxy-9-keto system in the products (CXIII), (CXV), (CXVIII)and (CXVII). Particularly useful for this purpose are thetetrahydropyranyl group and various trialkylsilyl groups (e.g.,dimethylisopropylsilyl, trimethylsilyl, dimethyl-t-butylsilyl and thelike. ##SPC14##

In accordance with the above reaction scheme the 3,4-epoxylactol (CV)[E. J. Corey and R. Noyori, Tetrahydron Letters, 311 (1970)] is treatedwith the ylide (CVI) to give the 3,4-epoxycyclopentanol (CVII) bearingthe α-chain of the prostaglandin 2 series. Oxidation (for example withH₂ CrO₄.-H₂ SO₄ -ether or Jones reagent) of (CVII) provides the epoxyketone (CVIII), mild base treatment of which results in the initialformation of the 4-hydroxycyclopent-2-en-1-one (CXI) and the isomeric3-hydroxycyclopent-4-en-1-one (CX) as a mixture. Further treatment ofthis mixture with dilute base under mild conditions (preferably pH10.3-10.6 for 24 hours) results in the isomerization of the 3-hydroxyisomer (CX) to the desired (CXI). We believe that the transformation ofthe epoxy ketone (CVIII) to the hydroxycyclopentenones (CX) and (CXI)and the isomerization of (CX) to (CXI) may take place through theintermediacy of the 3,4-diol (CIX). It is also conceivable thatisomerizaton of (CX) to (CXI) procedes via the epoxy derivative (CVIII)or the corresponding α-epoxide (CXIb); it is further conceivable that(CVIII) procedes to (CX) and (CXI) directly without the intermediacy of(CIX). Another possible intermediate for the isomerization of (CX) to(CXI) is the corresponding diene (CXIa). The preparation of (CXI) isalso possible via the α-epoxide series from (CXIc) via the α-epoxidecorresponding to (CVII) and (CVIII) such as (CXIb) or via a mixture ofthe α and β epoxides. In practice, it is most convenient to utilize amixture of α- and β-epoxides (CXIc and CV). The hydroxy and acidfunction is the 4-hydroxycyclopentenones (CXI) are then appropriatelyblocked to give (CXII). Appropriate blocking groups aretetrahydropyranyl, trimethylsilyl, dimethyl-isopropylsilyl,dimethyl-t-butylsilyl and the like. Treatment of (CXII) with the lithioalanate (CXIV) or its equivalent (see the discussion hereinabove forFlowsheets K and E) gives the conjugate addition product (CXIII) inwhich the configuration at C₈ is undetermined. Mild acid treatment, forexample with acetic acid:tetrahydrofuran:water,(4:2:1), of (CXIII)results in the removal of blocking groups, and if necessaryequilibration to the all-trans configuration, to give prostaglandin E₂(CXV). Similarly treatment of (CXII) with the lithio alanate (CXVI)gives prostaglandin E₃ (CXVII).

Substitution in Flowsheet N, of ylide (CXIX), wherein p is ashereinabove defined, for the ylide (CVI) provides, by transformationsanalogous to those described in Flowsheet N [(CV) to (CXI) and (CXII)],the 4-hydroxycyclopent-2-en-1-ones (CXX) and their blocked ether-esters(CXXI). These novel and useful intermediates are a part of the presentinvention. ##SPC15##

The 8β-lower alkyl group (R'₇) is introduced as illustrated in FlowsheetO below via the bromomagnesium enolate (CXXV). This novel and usefulintermediate is obtained by conjugate addition of the 1-alkenyl Grignardreagent [(CXXIII) + (CXXIV)], preferably prepared at about 35°C., to thecycloalkenone (CXXII) in the presence of a catalyst such as thetri-n-butylphosphine cuprous iodide complex as described hereinabove inconnection with Flowsheets G and H. It is also possible to utilize forthese purposes in an analogous manner the magnesio enolate (CXXVIII)obtained by conjugate addition of Grignard (XLII) to cycloalkenone (XLI)as described hereinabove in connection with Flowsheet F, in which casethe 13,14-dihydro derivative of this invention are obtained. InFlowsheet O below, n, Z, R₃, R'₃, R'₂, W₂, R₂, Q and X are ashereinabove defined and R'₇ is an alkyl group having up to 3 carbonatoms. When the magnesio enolate (CXXV) is treated with a lower alkylhalide, e.g., methyl iodide, it undergoes alkylation at the 8β-siteproviding, after deblocking of the 15-oxy group in intermediate (CXXVI),the 8β-alkyl derivative (CXXVII). In the instance of alkyl esters,saponification gives the corresponding carboxylic acids (CXXVII, R₃=OH). The compounds corresponding to (CXXVII) wherein C₁₃ -C₁₄ is acis-vinylene double bond are preferably prepared by utilizing the vinylGrignard reagent prepared at temperatures in the range of 70°-75°C., asdiscussed hereinabove (Flowsheets G and H).

Also obtained from the alkylation of (CXXV) is the 8α-alkyl-8-isoderivative corresponding to (CXXVI), which after deblocking provides the8α-alkyl-8-iso-products (CXXIX). Usually the 8α-product is formed to asignificantly lesser extent than the 8β-product (CXXVI). The 8α and 8βproducts are seperable from each other by the usual techniques ofchromatography. ##SPC16##

Application of the 8-alkylation process to the 11-oxy series providesthe novel compounds of formula (CXXX), wherein R₁, R₂, R₆, Y and C₁₃-C₁₄ are as hereinabove defined and wherein R'₇ is an alkyl group havingup to 3 carbon atoms, R₈ is selected from the group consisting ofhydrogen, lower alkanoyl, tetrahydropyranyl and tri-lower alkylsilylgroups, R₉ is selected from the group consisting of hydroxy, alkoxyhaving from 1 to 12 carbon atoms, tetrahydropyranyloxy and tri-loweralkyl silyloxy groups, Z₂ is a divalent radical selected from the groupconsisting of those of the formulae: ##EQU15## wherein m, p, R₄ and R₅are as hereinabove defined; and the moiety ##EQU16## when Y is ##EQU17##can also be the divalent radical ##EQU18## with the proviso that onlyone unsaturated bond can be directly adjacent to C₁₅ ; and with thesecond proviso that when R₆ is alkyl then R₁ is hydrogen: and with thethird proviso that the groups attached to C₈ may be in the 8β-alkyl(8-iso) configuration: ##EQU19##

The novel compounds of formula (CXXX) are also embraced by thisinvention. The preparation of these compounds may be illustrated by thereaction sequence of Flowsheet P below, wherein R₉, Z₂, W₂, R"₂, R'₇ andR₃ are as hereinabove defined and R'₈ has all the possibilities definedabove for R₈ except that it is not hydrogen. ##SPC17##

In accordance with the sequence of Flowsheet P above, treatment of theether-ester 4-oxycyclopentenone (CXXXI) with the 1-alkylene Grignardreagents [(CXXIII) + (CXXIV)] (see Flowsheet O) gives the bromomagnesioenolate (CXXXII). This operation also results in the introduction of thetrans C₁₃ -C₁₄ double bond (as shown in CXXXII), as well as thecorresponding compound with the cis-double bond. The trans bond isfavored when the Grignard is prepared at lower temperatures, about35°C.; the cis-bond at higher temperatures, about 70°-75°C. This pointis more fully discussed above in connection with Flowsheets G and H. Themagnesio enolate (CXXXII) is a key intermediate and when it is treatedwith a lower alkyl halide, e.g. methyliodide, it undergoes alkylation togive the 8β-lower alkyl derivative (CXXXIII). Deblocking of the15-hydroxy blocking group (e.g., triphenylmethyl), and of the 11-hydroxytetrahydropyranyl or trialkylsilyl ether blocking groups as well as ofthe tetrahydropyranyl or trialkyl silyl esters is accomplished undermild acid conditions, e.g. heating at 45°C. for 3.5 hours in a solventsystem consisting of acetic acid:tetrahydrofuran:water (4:2:1). Thisprocedure provides (CXXXV). The compounds of structure (CXXXV) or(CXXXIII) can be converted to 8β-alkyl prostaglandins of the A class(CXXXIV) by treatment with acid or base, a preferred procedure involvestreatment in tetrahydrofuran:water (2:1) solvent 0.5N in hydrochloricacid for about seventy hours at ambient temperatures.

The novel compounds of this invention represented by formula (CXXXIV)and related compounds are particularly interesting sunce they represent"stabilized" prostaglandin A types, which cannot rearrange to thebiologically relatively inactive prostaglandins of the B series.

Utilization of Grignard (XLII) (see Flowsheet F, hereinabove) in thesequence of Flowsheet P provides the compounds of (CXXX) wherein C₁₃-C₁₄ is ethylene. Provided there are no other double bonds in themolecule these substances can also be obtained by catalytichydrogenation of the compounds represented by formula (CXXXV).

The alkylation process described above for Flowsheets O and P also givesthe corresponding 8α-alkyl derivatives which are separable from the8β-alkyl isomer by chromatography. Thus, for example, in Flowsheet Otreatment of enolate (CXXV) with R'₇ I gives not only the 8β-alkylproduct (CXXVI) as shown, but there also is obtained the 8α-alkylderivative (CXXVI) shown below. In Flowsheet P, alkylation of enolate(CXXXII) also provides, in addition to (CXXXIII) shown, the8α-alkyl-8-iso product (CXXXVII), shown below. These 8α-alkyl-8-isoderivatives can be deblocked and carried through the same series oftransformation shown for the 8β-derivatives (CXXVI) and (CXXXIII) inFlowsheets O and P, respectively. These novel 8α-alkyl-8-iso derivativesand their transformation products are also a part of this invention, asare the key intermediate enolates represented by structures (CXXV) and(CXXXII). ##SPC18##

The novel compounds of the present invention have potential utility ashypotensive agents, anti-ulcer agents, agents for the treatment ofgastric hypersecretion and gastric erosion, bronchodilators,antimicrobial agents, anticonvulsants, abortifacients, agents for theinduction of labor, agents for the induction of menses,fertility-controlling agents, central nervous system regulatory agents,analgesic agents, salt and water-retention regulatory agents, diuretics,fat metabolic regulatory agents, serum-cholesterol lowering agents,anti-inflammatory agents and as agents for the inhibition of plateletaggragation, and for the treatment of periodontal disease, glaucoma,uveitis, sickle cell anemia and psoriasis. Certain of the novelcompounds of this invention possess utility as intermediates for thepreparation of other of the novel compounds of this invention.

The compounds of this invention provide protection against theulcerogenic properties of indomethacin. This assay was carried out inthe following manner.

Rats were starved for 48 hours (water was given ad libitum).Indomethacin (20 mg./kg. of body weight) was administered by thesubutaneous route and one-half the dose of the test compound wasadministered by gavage at the same time. After three hours, the secondhalf of the test compound was administered also by Gavage. Five hoursafter the administration of indomethacin the animals were decapitatedand the stomachs removed. The stomachs were washed with distilled water,blotted on gauze, cut along the larger curvature, and the contentsrinsed with distilled water. The stomachs were spread out, pinned on acork and visualized under magnifying glass for ulcers. The criteria forscoring of ulcers was as previously reported. [Abdel-Galil et al. Brit.J. Pharmac. Chemotherapy 33:1-14 (1968)].

    ______________________________________                                        Score                                                                         ______________________________________                                        0        Normal stomach                                                       1        Petechial hemorrhage or pin point ulcer                              2        1 or 2 small ulcers                                                  3        Many ulcers, a few large                                             4        Many ulcers, mainly large                                            ______________________________________                                    

Control animals treated with indomethacin but not test compoundconsistently give scores of about 3.0-3.5. Control animals treated withneither indomethacin nor test compound give scores of about 0.5-0.8. Theresults obtained in this assay with typical compounds of the presentinvention are set forth in Table 1 below. Compounds producing a score of2.5 or lower are considered to be active.

                  TABLE I                                                         ______________________________________                                                   Total Oral                                                                    dose; mg./kg.                                                                 of body   Score                                                    Compound     weight      Treated  Control                                     ______________________________________                                        9-oxo-15-hydroxy-                                                             16-ethyl-13-trans-                                                            prostenoic acid                                                                            25          1.7      3.2                                         9-oxo-15-hydroxy-                                                             13-cis-prostenoic                                                             acid         100         1.3      3.0                                         9-oxo-15-hydroxy-                                                             2-ethyl-13-trans-                                                             prostenoic acid                                                                            50          2.2      3.0                                         9-oxo-8β-methyl-                                                         15-hydroxy-13-                                                                trans-prostenoic                                                              acid         12.5        2.0      3.0                                         9-oxo-3-thia-15-                                                              hydroxy-13-trans-                                                             prostenoic acid                                                                            25          1.8      3.2                                         9-oxo-3-thia-15-                                                              epi-hydroxy-13-                                                               trans-prostenoic                                                              acid         25          2.3      3.2                                         ______________________________________                                    

The novel compounds of the present invention are also effectiveinhibitors of gastric acid secretion and of ulcer development inexperimental animals, and thus are potentially valuable as agents forthe control of gastric acid secretion and of gastric erosion and asanti-ulcer agents. Gastric acid secretion inhibitory action is usuallymeasured by the "Shay rat" procedure .sup.(1,2) with some modificationsas follows.

The rats (male, CFE strain) were starved for 48 hours (water was givenad libitum) to permit evacuation of stomach contents. On the morning ofthe experiment, under ether anesthesia, the abdominal region was shavedand a midline incision (1-11/2") was made with a scapel. With the helpof a closed curved hermostate the duodenum was picked up. Upon gettingthe duodenum into view, fingers were used to pull the stomach throughthe opening, the stomach was then gently manipulated with fingers to ridthe stomach of air and residual matter which were pushed through thepylorus. Two-5 inch sutures were drawn under the pyloric-duodenalpuncture. A ligature, at the juncture was formed with one of thethreads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./mg. body weight, wereinjected into the duodenum as close as possible to the first ligature.After injecton the second ligature was tightened below the injectionsite to minimize leakage. The stomach was placed back through theopening into the abdominal cavity, the area of incision was washed withsaline and the incision was closed with autoclips. (occasionally,instead of an intraduodenal injection, animals were dosed by the oral orsubcutaneous route. In the latter case, dosing was done thirty to sixtyminutes before the operation.)

Three hours later, the rats were decapitated and exanguinated, takingcare that blood did not drain into the estophagus. The abdominal cavitywas exposed by cutting with scissors and the esophagus close to thestomach was clamped off with a hemostat, the stomach was removed bycutting above the hemostat (the esophagus was cut) and between the twosutures. Extraneous tissue was removed, the stomach washed with salineand blotted on gauze. A slit was carefully made in the stomach which washeld over a funnel and the contents were collected in a centrifuge tube.The stomach was further cut along the outside edge and turned insideout. Two ml. H₂ O were used to wash the stomach contents into therespective centrifuged tube. The combined stomach contents and wash werethen centrifuged out for 10 minutes in the International Size 2Centrifuge (setting at 30). The supernatant was collected, volumemeasured and recorded, 2 drops of a phenolphthalein indicator (1% in 95%ethanol) were added and the solution was titrated with 0.02N NaOH (orwith 0.04N NaOH when large volumes of stomach contents were encountered)to pH 8.4 (because of usual coloring of the stomach contents,phenolphthalein was only used to permit visual indication that the endpoint was near) and the amount of acid present was calculated.

Compounds inducing inhibition of gastric acid secretion of 20% or morewere considered active. In a representative operation, and merely by wayof illustration, the results obtained with this assay with a typicalcompound of the present invention are given in Table 2, below.

                  TABLE 2                                                         ______________________________________                                                     Intraduodenal                                                                 dose, mg./kg. Percent                                            Compound     of body weight                                                                              Inhibition                                         ______________________________________                                        9-oxo-15-hydroxy-                                                             3,3-dimethyl-13-                                                              trans-prostenoic                                                              acid         100           51                                                 ______________________________________                                    

Bronchodilator activity was determined in guinea pigs againstbronchospasms elicited by intravenous injections of 5-hydroxytryptamine,histamine or acetylcholine by the Konzett procedure. [See J. Lulling, P.Lievens, F. El Sayed and J. Prignot, Arzeimittel-Forschung, 18 995(1968).]

In the Table which follows bronchodilater activity for representativecompounds of this invention against one or more of the three spasmogenicagents is expressed as an ED₅₀ determined from the results obtained withthree logarithemic cumulative intravenous doses.

                  TABLE 2A                                                        ______________________________________                                        Bronchodilator Activity (Konzett Assays)                                      ED.sub.50, mg./kg.                                                            Spasmogenic Agent                                                                         5-hydroxy-                                                        Compound    tryptamine histamine  choline                                     ______________________________________                                        9-oxo-15-hy-                                                                  droxy-16-ethyl                                                                13-trans-pro-                                                                             --         81.3 × 10.sup..sup.-6                                                              --                                          stenoic acid                                                                  9-oxo-15-hy-                                                                  droxy-13-cis-                                                                             106.sup..sup.-6                                                                          81.3 × 10.sup..sup.-6                                                              320 × 10.sup..sup.-6                  prostenoic                                                                    acid                                                                          9-oxo-15-hy-                                                                  droxy-2-ethyl-                                                                            329 × 10.sup.-.sup.6                                                               145 × 10.sup..sup.-6                                                               533 × 10.sup..sup.-6                  13-trans-pro-                                                                 stenoic acid                                                                  9-oxo-15-hy-                                                                  droxy-16-pro-                                                                 stynoic acid                                                                              50.8 × 10.sup..sup.-6                                                              92.6 × 10.sup..sup.-6                                                              320 × 10.sup..sup.-6                  ______________________________________                                    

The novel compounds of the present invention are useful as hypotensiveagents and their prostaglandin-like hypotensive activity wasdemonstrated in the following test procedure. This procedure is amodification of the technique described by Pike et al., Prostaglandins,Nobel Symposium 2, Stockholm, June, 1966; p. 165.

Male Wistar strain rats (Royal Hart Farms) averaging approximately 250grams in weight were fastened to rat boards in a supine position bymeans of canvas vests and limb ties. The femoral area was infiltratedsubcutaneously with lidocaine and the iliac artery and vein were exposedand cannulated. Arterial blood pressure (systolic/diastolic) wasrecorded using a Statham P₂₃ Db pressure, the animals were anethetizedbefore use with pentobarbital, 30 mg./kg. of body weight intravenously,and also were given hexamethoxium bitartrate, 2 mg./kg. of body weightintravenously. The test compounds were prepared by ultrasonic dispersionin a saline-Tween 80 vehicle. A constant intravenous dose volume of 0.5ml. was administered and test doses ranged from 0.1 to 10.0 mg./kg. ofbody weight. Increasing or decreasing doses were selected depending onthe dose response obtained. In Table 2B below are set forth the minimaldoses required to produce a decrease of about 10 mm. in diastolic bloodpressure for typical compounds of the present invention.

                  TABLE 2B                                                        ______________________________________                                        HYPOTENSIVE ACTIVITY                                                                             Minimal effective                                                             hypotensive dose                                           Compound           (mg./kg. of body wt.)                                      ______________________________________                                        2-ethyl-9-oxo-15-                                                             hydroxy-13-trans-pro-                                                         stenoic acid       <2                                                         2-ethyl-9-oxo-15-epi-                                                         hydroxy-13-trans-pro-                                                         stenoic acid       2-4                                                        2-ethyl-9-oxo-15-                                                             hydroxy-prostanoic                                                            acid               0.2                                                        2-methyl-9-oxo-15-epi-                                                        hydroxy-13-trans-pro-                                                         stenoic acid       2                                                          2-methyl-9-oxo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid       2                                                          8β-methyl-9-oxo-15-                                                      hydroxy-13-trans-                                                             prostenoic acid    2                                                          9-oxo-15-hydroxy-16-                                                          ethyl-13-trans-pro-                                                           stenoic acid       <8                                                         3,3-dimethyl-9-oxo-15-                                                        hydroxy-13-trans-pro-                                                         stenoic acid       8                                                          9-oxo-15-hydroxy-13-cis-                                                      prostenoic acid    2-4                                                        9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid       <2                                                         9-oxo-15-hydroxy-16-                                                          prostynoic acid    2                                                          9-oxo-15-hydroxy-5-cis,                                                       13-trans,17-cis-prosta-                                                       trienoic acid      <2                                                         3-oxo-9-oxo-15-hydroxy-                                                       13-trans-prostenoic                                                           acid               <2                                                         3-oxa-9-oxo-15-epi-                                                           hydroxy-13-trans-pro                                                          stenoic acid       1-2                                                        3-thia-9-oxo-15-hydroxy-                                                      13-trans-prostenoic                                                           acid               2                                                          3-thia-9-oxo-15-epi-                                                          hydroxy-13-trans-                                                             prostenoic acid    2                                                          9-oxo-15-hydroxy-16-                                                          trans-prostenoic acid                                                                            <2                                                         2-phenyl-9-oxo-15-                                                            hydroxy-13-trans-                                                             prostenoic acid    8                                                          2-phenyl-9-oxo-15-epi-                                                        hydroxy-13-trans-pro-                                                         stenoic acid       2-8                                                        2-fluoro-9-oxo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid       8                                                          7a,7b-bishomo-9-oxo-15-                                                       hydroxy-13-trans-                                                             prostenoic acid    <8                                                         9-oxo-10a-homo-15-                                                            hydroxy-13-trans-pro-                                                         stenoic acid       2                                                          9-oxo-10a-homo-15-epi-                                                        hydroxy-13-trans-                                                             prostenoic acid    2                                                          9-oxo-15-hydroxy-15-                                                          methyl-5-cis,13-trans,                                                        17-cis-prostatrienoic                                                         acid               <2                                                         Ethyl 3-oxa-9-oxo-15-                                                         hydroxy-13-trans-                                                             prostenoate        0.2                                                        Ethyl 3-oxa-9-oxo-15-                                                         epi-hydroxy-13-trans-                                                         prostenoate        0.2                                                        Ethyl 9-oxo-10a-homo-                                                         15-hydroxy-13-trans-                                                          prostenoate        2                                                          9-oxo-15-hydroxy-16,16-                                                       dimethyl-13-trans-                                                            prostenoic acid    < 2                                                        9-oxo-15-hydroxy-17,17-                                                       dimethyl-13-trans-                                                            prostenoic acid    2                                                          3-thia-9-oxo-15-hydroxy-                                                      16,16-dimethyl-13-                                                            trans-prostenoic acid                                                                            <2                                                         3-oxa-9-oxo-15-hydroxy-                                                       16,16-dimethyl-13-                                                            trans-prostenoic acid                                                                            <2                                                         ______________________________________                                    

This invention will be described in greater detail in conjunction withthe following specific examples. In these examples it is to be notedthat Example 724 follows directly after Example 699.

In the examples which follow reference to 15-hydroxy or 15-oxyderivatives, unless otherwise indicated is inclusive of both the 15-epiand 15-normal racemates. In addition, all possible antipodes resultingfrom asymetry at C₈, C₁₂ and elsewhere in the prostenoic acid moleculeare included.

EXAMPLE 1 Preparation of2-carbalkoxy(methyl/ethyl)-2-(4-carbethoxybutyl)cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolatein dimethoxyethane, prepared from 187 g. (1.248 moles) of2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g.(1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 1. ofdimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl5-iodovalerate. The reaction mixture is stirred and heated at reflux for18 hours. The mixture is cooled and filtered. The solvent is removedfrom the filtrate by evaporation and the residue is poured into dilutehydrochloric acid and extracted with ether. The combined extracts arewashed with water and saline, dried over magnesium sulfate andevaporated to give an oil. The oil is distilled under reduced pressureto give 274 g. of a light yellow oil, b.p. 140°-143°C. (0.17 mm).

EXAMPLE 2 Preparation of 2-(4-carboxybutyl)cyclopentan-1-one

A stirred mixture of 274 g. of 2-carbalkoxy(mixed methyl and ethylesters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux for20 hours. Solution occurs in approximately 1/2 hour. The solution iscooled and diluted with water and extracted with ether. The combinedextracts are washed with saline and dried over magnesium sulfate andevaporated. The residue is evaporated twice with toluene to give 144 g.of an oil.

EXAMPLE 3 Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mole) of2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18hours. The solvent is evaporated and the residue is dissolved in ether.The ether solution is washed with saline, dilute sodium bicarbonatesolution and again with saline, dried over magnesium sulfate andevaporated. The oil is distilled under reduced pressure to give 149 g.of a colorless oil, b.p. 106°-109°C. (0.23 mm).

EXAMPLE 4 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanonecarboxylate (mixed methyl and ethyl esters) with sodium hydride indimethoxyethane followed by ethyl 4-iodobutyrate gives a yellow oil,b.p. 136°-137°C. (0.16 mm).

EXAMPLE 5 Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixedmethyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one(Example 4) with a 20% hydrochloric acid and acetic acid mixture gives ayellow oil.

EXAMPLE 6 Preparation of 2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 3, treatment of2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluenesulfonicacid monohydrate in ethanol gives a colorless oil, b.p. 93°C. (0.10 mm).

EXAMPLE 7 Preparation of ethyl and methyl2-(6-carbethoxyhexyl)-1-cyclopentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentanonecarboxylate is reacted with ethyl 7-bromoheptanoate to furnish thesubject product, b.p. 147°C. (0.09 mm).

EXAMPLE 8 Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) ishydrolyzed to furnish the subject product, b.p. 143°C. (0.05 mm).

EXAMPLE 9 Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3,2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnishthe subject product, b.p. 110°C. (0.03 mm).

EXAMPLE 10 Preparation of 1-acetoxy-2-(6-carbethoxyhexly)cyclopent-1-one

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one(Example 9) in 250 ml. of acetic anhydride containing 0.940 g. ofp-toluenesulfonic acid monohydrate is heated to boiling under partialreflux allowing distillate at 118°C. or less (i.e., acetic acid) toescape through a Vigreaux column equipped with a condenser to collectthe distillate. After 16 hours, during which period acetic anhydride isadded in portions in order to keep the solvent level at at least 100ml., the solution is cooled and poured cautiously into a stirred coldmixture of saturated sodium bicarbonate solution (400 ml.) and hexane(250 ml.). The resulting mixture is stirred for an additional 30 minutesduring which period solid sodium bicarbonate is added periodically toinsure a basic solution. The hexane layer is separated and washed withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness. Distillation of the residual oil gives 102g. (87%) of pale yellow oil, b.p. 118°C. (0.07 mm).

EXAMPLE 11 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-one

In the manner described in Example 10, treatment of2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with aceticanhydride and p-toluenesulfonic acid monohydrate gives a yellow oil,b.p. 98°-103°C. (0.35 mm).

EXAMPLE 12 Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene

In the manner described in Example 10, treatment of2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydrideand p-toluenesulfonic acid monohydrate gives a yellow oil, b.p.109°-110°C. (0.37 mm).

EXAMPLE 13 Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene (Example 10) in 150 ml.of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooledin an ice bath, is added dropwise over a period of about 30 minutes, asolution of 30 g. of bromine in 50 ml. of carbon tetrachloride. Afterstirring for an additional 45 minutes the chloroform layer is separatedand washed successively with dilute sodium thiosulfate solution,saturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylformamide andadded to a mixture of 33 g. of lithium bromide and 32 g. of lithiumcarbonate in 375 ml. of N,N-dimethylformamide, previously dried byrefluxing with 375 ml. of benzene under a Dean-Stark apparatus followedby distillation of the benzene. The mixture is stirred at the refluxtemperature for 30 minutes, then cooled and poured into 850 ml. ofice-cold water. The resulting mixture is acidified (cautiously) with 4Nhydrochloric acid and extracted with ether 3 times. The combined etherextracts are washed with saturated sodium chloride solution, dried withanhydrous magnesium sulfate and taken to dryness under reduced pressureto afford 41.5 g. of an amber oil. In order to convert any isomericmaterial to the desired product, 41.5 g. of the above material istreated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450 ml.of absolute alcohol at the reflux temperature for 18 hours. The solutionis taken to dryness under reduced pressure. The resulting gum isdissolved in ether and washed with saturated sodium bicarbonatesolution, saturated sodium chloride solution, dried with anhydrousmagnesium sulfate and taken to dryness under reduced pressure. Theresidual oil is distilled to give 30.2 g. of product; b.p. 118°C. (0.05mm); λ_(max) ^(MeOH) 229 mμ (E9950): λ_(max) 5.75, 5.85, 6.15, 8.45 μ;vapor phase chromatography shows 99% product, containing 1%2-(6-carbethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containingapproximately 5% of the saturated analogue, and 7.67 g. (10 molepercent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol isstirred at ambient temperatures for 18 hours and is then refluxed for 1hour. The mixture is cooled, the solvent is evaporated, and the residueis taken up into 150 ml. of chloroform and passed through a column of450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield acolorless oil containing <0.5% of the saturated impurity.

EXAMPLE 14 Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-one (Example 11) followed bydehydrobromination with lithium bromide and lithium carbonate isproductive of the subject compound.

EXAMPLE 15 Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene (Example 12) with bromineand subsequent treatment of the brominated product with a mixture oflithium bromide and lithium carbonate in N,N-dimethylformamide isproductive of the subject compound. Treatment of this product withp-carboxyphenylhydrazine by the procedure of Example 13 furnishes aproduct which contains less than 0.5% of the corresponding saturatedketone.

EXAMPLE 16 Preparation of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13 ) and 15.0 g. (0.180mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol isadded 25 ml. of pyridine and the resulting solution is stirred for 20hours at ambient temperatures. The solvent is evaporated and the residueis partitioned between water and diethyl ether. The organic phase iswashed with water and saturated brine, dried (Na₂ SO₄), and the solventis evaporated to yield an oil. Distillation yields 38.7 g. of acolorless oil, b.p. 115°-118°C. (0.075 mm). IR (film): 1740, 1627, 1053,890 cm.sup.⁻¹. λ_(max) (MeOH) 243 (13,000). NMRδ (CDCl₃): 3.89.

EXAMPLE 17 Preparation of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200ml. of benzene under nitrogen is added dropwise 225 ml. of a 25%solution of diisobutyl aluminum hydride in hexane. The resultingsolution is stirred for 2 hours at 0°-5°C., poured onto ice and dilutehydrochloric acid, and the aqueous phase is saturated with sodiumchloride. The organic phase is separated, washed with saturated brine,dried (Na₂ SO₄), and evaporated to yield an oil. The latter is dissolvedin 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p.62°-64°C. IR (KBr) 3260, 1630, 1059, 893 cm.sup.⁻¹ : λ_(max) 243(14,200). NMR (CDCl₃)δ: 2.37.

EXAMPLE 18 Preparation of1-methoximino-2-(7-p-toluenesulfonyloxyheptyl)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml.of dry pyridine at 0°C. is added 8.45 g. (0.0444 mole) ofp-toluenesulfonyl chloride and the resulting solution is chilled at 5°C.overnight. The mixture is partitioned between 300 ml. of ice water anddiethyl ether. The organic phase is washed with 1:1 ice coldhydrochloric acid, cold water, and cold saturated brine, dried (NaSO₄/K₂ CO₃), and evaporated under reduced pressure at room temperature toyield an oil. The latter is dissolved in 600 ml. of hexane, treated with0.5 g. of Darco, filtered and evaporated to yield 7.7 g. of a colorlessoil. IR (film) 1600, 1192, 1182, 1053, 890 cm.sup.⁻¹. λ_(max) (MeOH) 228and 243.

EXAMPLE 19 Preparation of1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847g. (0.0368 g. atoms) of sodium, 100 ml. of absolute ethanol, and 7.05 g.(0.0440 mole) of diethyl malonate is added 7.7 g. of tosylate of Example18 and the mixture is refluxed for 2 hours under a nitrogen atmosphere.The mixture is partitioned between cold dilute hydrochloric acid anddiethyl ether, and the organic phase is washed with water and saturatedbrine, dried (Na₂ SO₄), and evaporated to yield an oil. The excessdiethyl malonate is distilled off under reduced pressure to yield 6.45g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm.sup.⁻¹.

EXAMPLE 20 Preparation of1-methoximino-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of Example 19 and 6.72 g. ofpotassium hydroxide in 150 ml. of 1:1 aqueous methanol is refluxed for 1hour, cooled, and is partitioned between water and diethyl ether. Theaqueous phase is acidified with hydrochloric acid, extracted with ether,and the organic phase is washed with water and saturated brine, dried(Na₂ SO₄) and evaporated to yield a solid. The solid is crystallizedfrom benzene to yield 4.15 g. of tan crystals, m.p. 135°-137°C. (-CO₂).

EXAMPLE 21 Preparation of1-methoximino-2-(8-carboxyoctyl)-2-cyclopentene

A solution of 3.926 g. (0.0126 mole) of the diacid of Example 20 in 20ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yielda tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm.sup.⁻¹.

EXAMPLE 22 Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5 hours with 55 ml.of acetone and 20 ml. of 2N hydrochloric acid. The mixture is cooled,the solvent is evaporated, and the residue is partitioned between waterand diethyl ether. The organic phase is washed with water and saturatedbrine, dried (Na₂ SO₄), and evaporated to yield a tan solid. IR (KBr)1745, 1665 cm.sup.⁻¹. λ_(max) (MeOH) 228 (12,600).

EXAMPLE 23 Preparation of 2-(8-carbethoxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. ofabsolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonicacid for 6 hours, cooled, and the solvent is evaporated. The resultingoil is dissolved in 3:1 benzene-ether and the solution is passed througha column of 100 g. of Florisil. The filtrate is evaporated and theresidue is distilled to yield 2.97 g. of a colorless oil, b.p.137°-139°C. (0.05 Torr).

EXAMPLE 24 Preparation of 2-(4-carbethoxybutyl)-2-cyclopentenonemethoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenone (Example 15) withmethoxyamine hydrochloride in the manner described in Example 16 givesan oil, b.p. 107°-109°C. (0.05 mm). IR (film): 1740, 1628, 1050, 885cm.sup.⁻¹. λ_(max) (MeOH) 243 (13,600).

EXAMPLE 25 Preparation of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenomethoxime (Example 24)with diisobutyl aluminum hydride in the manner described in Example 17gives crystals, m.p. 33°-35°C. IR (KBr) 3420, 1630, 1050, 886 cm.sup.⁻¹.λ_(max) ^(MeOH) 243 (12,020).

EXAMPLE 26 Preparation of2-(5-p-toluenesulfonyloxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime (Example 25)with p-toluenesulfonyl chloride in pyridine in the manner described inExample 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885cm.sup.⁻¹.

EXAMPLE 27 Preparation of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenonemethoxime

To a solution of sodio diethyl ethylmalonate, prepared from 1.63 g.(0.0387 mole) of sodium hydride in mineral oil (57.2%), 100 ml. ofethylene glycol dimethyl ether and 8.5 g. (0.0452 mole) of etyl diethylmalonate, is added 7.5 g. of tosylate from Example 26 in 20 ml. ofethylene glycol dimethyl ether and the mixture is refluxed for 3 hoursand then allowed to stand at room temperature for 18 hours undernitrogen atmosphere. The reaction mixture is piltered and most of thesolvent is removed. The mixture is partitioned between cold dilutehydrochloric acid and diethyl ether, and the organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yieldan oil. The excess ethyl diethyl malonate is distilled off under reducedpressure to yield 6.7 g. of a yellow oil. IR (film) 1755, 1728, 1627,1050, 885 cm.sup.⁻¹.

EXAMPLE 28 Preparation of 2-(6,6-dicarboxyoctyl)-2-cyclopentenonemethoxime

Treatment of 2-(6,6-dicarbethoxyoctyl)-2-cyclopenteno methoxime (Example26) with potassium hydroxide, and 1:1 aqueous methanol in the mannerdescribed in Example 20 gives a light yellow oil.

EXAMPLE 29 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime

In the manner described in Example 21, treatment of2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime (Example 28) withxylene at reflux for 18 hours gives a yellow oil.

EXAMPLE 30 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime (Example 29)with acetone and 2N hydrochloric acid in the manner described in Example22 gives a light yellow oil.

EXAMPLE 31 Preparation of 2-(6-carbethoxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone (Example 30) withthionyl chloride and then treatment of the acid chloride with ethanol inthe usual manner gives an amber oil. The oil is placed on amagnesia-silica gel column and eluted with 3:1 benzene-ether. Thesolvent is removed and the residue is distilled, b.p. 122°C. (0.06 mm).

EXAMPLE 32 Preparation of diethyl1,1-dimethyl-5-tetrahydropyranylpentylmalonate

To 486 mg. (0.02 g.-atoms) of magnesium in 5 ml. of toluene containingone molar equivalent of tetrahydrofuran per equivalent of magnesium andone percent iodine (calculated in weight of magnesium) is added dropwise3.86 g. (0.02 mole) of 4-chloro-1-tetrahydropyranyloxybutane over aperiod of one hour with stirring, under nitrogen at 70°C. The reactionmixture is stirred at 70°C. for 4 hours. This reagent is then addeddropwise to 3 g. (0.015 mole) of ethyl isopropylidenemalonate in 40 ml.of tetrahydrofuran containing 392 mg. of tetrakis[iodo(tri-n-butylphosphine)copper (I)] and stirred at room temperaturefor 2 hours. The reaction mixture is poured into cold dilutehydrochloric acid and extracted with ether. The ether extract is driedover magnesium sulfate and concentrated to give 5.92 g. of subjectproduct as an oil.

EXAMPLE 33 Preparation of diethyl 1,1-dimethyl-5-hydroxypentylmalonate

A solution of 3.5 g. (0.01 mole) of diethyl1,1-dimethyl-5-tetrahydrofuranyloxypentylmalonate in 70 ml. of ethanolcontaining 3 ml. of hydrochloric acid is allowed to stir at roomtemperature for 18 hours. The solution if concentrated, diluted withwater and extracted with ether. The ether extract is washed with water,dried over magnesium sulfate and concentrated to give 3.262 g. of alight yellow oil. The oil is purified by distillation, b.p. 116°-117°C.(0.05 mm).

EXAMPLE 34 Preparation of 3,3-dimethyl-7-hydroxyheptanoic acid

A mixture of 32 g. (0.177 mole) of diethyl1,1-dimethyl-5-hydroxypentylmalonate, 25 g. of potassium hydroxide and600 ml. of methanol-water (1:1) is heated at reflux for 8 hours and thenallowed to stand at room temperature for 18 hours. The methanol isremoved, diluted with water and the reaction mixture is acidified withconcentrated hydrochloric acid. The mixture is extracted with ether. Theextract is washed with water and saline, dried over anhydrous magnesiumsulfate and concentrated to give 27 g. of1,1-dimethyl-5-hydroxypentylmalonic acid. This crude oil is dissolved in200 ml. of bis-(2-methoxyethyl)ether and is heated at reflux for 4 hoursand then allowed to stand at room temperature overnight. The solvent isremoved and the reaction mixture is diluted with water and extractedwith ether. The organic solution is washed with saline, dried overmagnesium sulfate and concentrated to give 18 g. of product as an oil.

EXAMPLE 35 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3.484 g. (0.02 mole) of 3,3-dimethyl-7-hydroxyheptanoicacid in 25 ml. of chloroform containing 3 drops of dimethylformamide isadded 5.8 ml. (0.08 mole) of thionyl chloride and the solution is thenheated at reflux for 3-4 hours. The solution is concentrated to give theintermediate 3,3-dimethyl-7-chloro-1-heptanoyl chloride. The acidchloride is dissolved in a minimum amount of benzene and added slowly to20 ml. benzene, 10 ml. of ethanol and 2.65 ml. of collidine. Thesolution is heated at reflux for 1 hour and then concentrated. Theresidue is dissolved in ether, washed with water, dilute sodiumbicarbonate solution and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 3.57 g. of product as ayellow oil.

EXAMPLE 36 Preparation of ethyl 3,3-dimethyl-7-iodoheptanoate

To a solution of 3.57 g. (0.0162 mole) of ethyl3,3-dimethyl-7-chloroheptanoate in 100 ml. of methyl ethyl ketone isadded 4 g. of sodium iodide and the mixture heated at reflux for 18hours. The reaction mixture is cooled, filtered and concentrated. Theresidue is partitioned between ether and water. The aqueous phase isextracted several times with ether. The extract is washed with sodiumbisulfate solution, water and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 4.182 g. of a yellow oil. Thematerial is purified by distillation, b.p. 86°-87°C. (0.18 Torr).

EXAMPLE 37 Preparation of2-carbalkoxy(methyl/ethyl)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by treatment of sodio cyclopentanonecarboxylate enolate with ethyl 3,3-dimethyl-7-iodoheptanoate by theprocedure described in Example 1.

EXAMPLE 38 Preparation of2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by decarbalkoxylation of 2-carbalkoxy (mixedmethyl and ethylester)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one by theprocedure described in Example 2.

EXAMPLE 39 Preparation of2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

Esterification of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one withethanol by the procedure described in Example 3 is productive of thesubject compound.

EXAMPLE 40 Preparation of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-one

This compound is prepared from1-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one and acetic anhydrideby the process described in Example 10.

EXAMPLE 41 Preparation of2-(6-carbethoxy-5,5-dimetylhexyl)cyclopent-2-en-1-one

This compound is prepared from1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene viabromination and dehydrobromination according to the procedure describedin Example 13.

EXAMPLE 42 Preparation of2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example16, 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-2-cyclopentenone (Example 14) and methoxyaminehydrochloride.

EXAMPLE 43 Preparation of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene anddiisobutylaluminum hydride.

EXAMPLE 44 Preparation of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 4.833 g. (0.0266 mole) of2-(4-hydroxypentane)-1-methoximino-2-cyclopentene in 50 ml. of drytetrahydrofuran under nitrogen is added 16.7 ml. of 1.6 molar n-butyllithium in hexane, dropwise. The reaction mixture is stirred for 0.5hour and then 4.85 g. (0.029 mole) of ethyl bromacetate is addeddropwise. The reaction mixture is stirred overnight at room temperatureand the refluxed for 1.5 hours. The reaction is cooled and poured intowater and extracted several times with ether. The ether extracts arewashed with saline, dried over magnesium sulfate, and concentrated. Theresidue is placed on an alumina column, chloroform being used as a washsolvent. The combined washings are concentrated to dryness to give 4.903g. of product an a yellow oil.

EXAMPLE 45 Preparation of 2-(6-carboxy-5-oxahyexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene with acetoneand 2N hydrochloric acid at reflux gives the subject compound as ayellow oil.

EXAMPLE 46 Preparation of 2-(6-carbethoxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 23, treatment of2-(6-carboxy-5-oxahexyl)-2-cyclopentenone with p-toluenesulfonic acid inethanol produces the subject product as a light yellow oil.

EXAMPLE 47 Preparation of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopenten

To a ice cold solution of 3.66 g. (0.02 mole) of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene (Example 43) in 50 ml.of 1,2-dimethoxyethane under nitrogen is added dropwise 17 ml. of 1.6 Mn-butyl lithium in hexane. The reaction mixture is stirred for half anhour and then the lithium salt of cloroacetic acid, prepared from 1.89g. (0.02 mole) of chloroacetic acid and 16 ml. of 1.6M n-butyl lithiumin 20 ml. of dimethoxyethane, is added and the reaction mixture isheated at reflux for 48 hours. The solvent is evaporated and the residueis partitioned between ether and water. The aqueous phase is acidifiedwith hydrochloric acid and extracted with ether. The organic phase iswashed with water and saturated saline solution, dried (MgSO₄) andevaporated to give 3.35 g. of a yellow oil.

EXAMPLE 48 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopenten-1-one

In the manner described in Example 22, treatment of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene (Example 47) withacetone and 2N hydrochloric acid at reflux gives the subject compound asa yellow oil.

EXAMPLE 49 Preparation of1-methoximino-2-(4-methanesulfonyloxybutyl)-2-cyclopentene

To a solution of 1.83 g. (0.01 mole) of1-methoximino-2-(4-hydroxybutyl)-2-cyclopentene (Example 43) in 10 ml.of methylene chloride containing 1.52 g. (0.015 mole) of triethylamineis added 1.265 g. (0.011 mole) of methanesulfonyl chloride over a periodof 5-10 minutes at -10-0°C. Stirring is continued for 15 minutes and thesolution is then washed with cold water, cold 10% hydrochloric acid,cold sodium bicarbonate solution, and cold saline solution. The organicphase is dried (MgSO₄) and conentrated to give an oil which solidifiesupon cooling. Crystallization from ether-petroleum ether (30°-60°C.)gives 1.797 g. of white crystals, m.p. 67°-68°C.

EXAMPLE 50 Preparation of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dryN,N-dimethylformamide is heated at 65°-70°C. for 3 hours. The cooledreaction mixture is poured into water and extracted with diethyl ether.The organic phase is washed with water and saturated saline solution,dried (MgSO₄), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 51

Preparation of 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 50) and 1 g.(0.025 mole) of sodium hydroxide in 50 ml. of 1:1 aqueous-ethanol isrefluxed for 48 hours, cooled, and partitioned between water and diethylether. The aqueous phase is acidified with hydrochloric acid, extractedwith diethyl ether, and the organic phase is washed with water andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.86 g.of a yellow oil. EXAMPLE 52 Preparation of2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole)1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 51) in 44 ml.of acetone and 13.1 ml. of 2N hydrochloric acid is refluxed for 5 hours.The solvent is partially evaporated and a solid precipitates and iscollected. Theresidue is extracted with diethyl ether and the organicphase is washed with saturated saline solution, dried (MgSO₄), andevaporated to yield additional solid. The combined solid material iscrystallized from ether/pet ether (30°-60°C) to yield crystallinematerial, m.p. 70°-72°C.

EXAMPLE 53 Preparation of 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of2-(5-carboxypentyl)-2-cyclopentenone (Example 52) and 90 mg. ofp-toluenesulfonic acid in 150 ml. of ethanol is refluxed for 18 hours.The solvent is evaporated and the residue is dissolved in ether. Theorganic phase is washed with water, sodium bicarbonate solution, andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.371g. of a light yellow oil.

EXAMPLE 54 Preparation of2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxycyopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0moles) of cyclopentanone carboxylate (methyl and ethyl esters) and 200g. (8.3 moles) of mineral oil free sodium hydride in 10 l. of1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate [M.E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947)], and 1200 g.(8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours.The mixture is cooled, concentrated to 4 l. and partitioned betweendilute hydrochloric acid and diethyl ether. The organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yield1920 g. of an oil.

EXAMPLE 55 Preparation of2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxypentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example54), 2.2 l. of glacial acetic, 1 l. of concentrated hydrochloric acid,and 1 l. of water is refluxed for 18 hours, cooled, and partitionedbetween saturated brine and benzene. The organic phase is washed withsaturated brine, dried (MgSO₄), and evaporated in vacuo to yield 3155 g.of an oil.

EXAMPLE 56 Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene Asolution of 400 g. (2.04 moles) of a mixture of2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone(Example 55) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 l. ofacetic anhydride is refluxed at a rate to maintain a steady distillationof acetic acid from the reaction through a helix-packed fractionationcolumn. The reaction is continued with the addition of acetic anhydrideto maintain a constant volume until complete conversion of startingmaterials to produce is evident. The mixture is cooled and partitionedbetween 2 l. of hexane and 3 l. of cold water containing solid sodiumbicarbonate to mantain a neutral pH. The organic phase is washed withsaturated brine, dried (MgSO₄), and evaporated to yield 452 g. of anoil. EXAMPLE 57 Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate, 3l. of water, and 2.5 l. of chloroform cooled to 5°C. is addedsimultaneously 1016 g. (4.0 moles) of1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 56) and asolution of 648 g. (4.05 moles) of bromine in 500 ml. of carbontetrachloride at a rate to maintain a temperature below 10°C. Themixture is stirred for half an hour after addition of the reagents andthe phases are then separated. The organic phase is washed with 2%sodium thiosulfate solution, water, and saturated brine, dried (MgSO₄),and evaporated in vacuo to an oil. The oil is immetiately added to arefluxing a slurry of 500 g. (5.0 moles) of calcium carbonaate in 2.5 lof N,N-dimethylacetamide under nitrogen and the mixture is then refluxedfor thirty minutes. The mixture is cooled, filtered, and partitionedbetween water and diethyl. The organic phase is washed with water andsaturated brine, dried (MgSO₄), and evaporated to yield 757 g. of anoil, b.p. 116°-118°C. (0.25 mm.).

EXAMPLE 58 Preparation of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16,2-(5-acetoxypentyl)-2-cyclopentenone (Example 57) is treated withmethoxyamine hydrochloride in pyridine and ethanol to yield the subjectcompound, b.p. 101°-103°C. (0.20 mm.).

EXAMPLE 59 Preparation of1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 58 ) and 56 g.(1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol isrefluxed for 2 hours and then cooled. The solvent is partially removedin vacuo and the residue is partitioned between saturated brine anddiethyl ether. The organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to yield an oil which crystallized, m.p.35°-36°C.

EXAMPLE 60 Preparation of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene (Example 59) and 7.6 g.(0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10°C.is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate tomaintain a temperature of -10° to 0°C. The mixture is then stirred for15 minutes and then poured into ice water. The organic phase is washedwith cold 10% hydrochloric acid, cold saturated sodium bicarbonatesolution, and cold saturated brine, dried (MgSO₄), and evaporated toyield a solid, m.p. 78°-80°C.

EXAMPLE 61 Preparation of1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of sodiodiethylmalonate in 1,2-dimethoxyethane, preparedfrom 248 g. (1.55 moles) of diethyl malonate and 17.2 g. (0.95 mole) ofmineral oil free sodium hydride in 1 l. of 1,2-dimethoxyethane undernitrogen, is added 170 g. (0.62 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)in 15.1 l. of 1,2-dimethoxyethane and the mixture is refluxed for 5hours. The mixture is cooled, filtered, and the solvent is evaporated.The residue is partitioned between cold dilute hydrochloric acid andwater, and the organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to remove solvent and excess diethyl malonate toyield 209 g. of an oil.

EXAMPLE 62 Preparation of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20,1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene is treated withpotassium hydroxide in 1:1 aqueous methanol and then hydrochloric acidto yield the desired compound as crystals from diethyl ether, m.p.110°-115°C.

EXAMPLE 63 Preparation of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. ofbis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, andevaporated to yield an oil. The latter is crystallized from hexane toyield 92 g. of solid, m.p. 70°-72°C.

EXAMPLE 64 Preparation of 2-(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatmemt of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 63) withacetone and 2N hydrochloric acid at reflux provides the subjectcompound.

EXAMPLE 65 Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 64)in the manner of Example 23 provides the subject compound.

EXAMPLE 66 Preparation of1-methoximino-2-(6-fluoro-6,6-dicarbethoxyhexyl)-2-cyclopentene

To a solution of sodiodiethyl fluoromalonate, prepared from 2.062 g.(0.0491 mole) of sodium hydride in mineral oil (57.2%), 40 ml. of dryN,N-dimethylformanide and 8.174 g. (0.0458 mole) of diethylfluoromalonate is added dropwise 11.32 g. (0.0413 mole) of1-methoximino-2-(5-methylsulfonyloxypentyl)-2-cyclopentene (Example 60)in 60 ml. of N,N-dimethylformamide. The mixture is reluxed for 2 hoursunder a nitrogen atmosphere. The mixture is concentrated and partitionedbetween cold dilute hydrochloric acid and diethyl ether, and the organicphase is washed with saturated brine, dried (MgSO₄), and evaporated toyield 13.631 g. (92%) of a yellow oil.

EXAMPLE 67 Preparation of1-methoximino-2-(6-fluoro,6,6-dicarboxyhexyl)-2-cyclopentene

A mixture of 13.631 g. of the diester of Example 66 and 16 g. ofpotassium hydroxide in 364 ml. of 1:1 aqueous methanol is refluxed for 5hours, cooled, concentrated, and is partitioned between water anddiethyl ether. The aqueous phase is acidified with hydrochloric acid,extracted with ether, and the organic phase is washed with saturatedbrine, dried (MgSO₄) and evaporated to yield a solid. The solid iscrystallized from diethyl ether petroleum ether (30°-60°C.) to give 10g. (90%) of white crystals, m.p. 143°-145°C. (--CO₂).

EXAMPLE 68 Preparation of1-methoximino-2-(6-fluoro-6-carboxyhexyl)-2-cyclopentene

A solution of 10 g. of the diacid of Example 67 in 60 ml. of2-methoxyethyl ether is refluxed for 7 hours, cooled, and evaporated toyield 8.5 g. (95%) of a tan solid. A sample is crystallized from diethylether-petroleum ether (30°-60°C.) to give white crystals, m.p.98°-100°C.

EXAMPLE 69 Preparation of2-(6-fluoro-6-carboxyhexyl)cyclopent-2-en-1-one

The acid methoxime (8.5 g.) from Example 68 is refluxed for 5 hours with180 ml. of acetone and 64 ml. of 2N hydrochloric acid. The mixture iscooled, the solvent is evaporated, and the residue is partitionedbetween water and diethyl ether. The organic phase is washed withsaturated brine, dried (MgSO₄) and evaporated to yield 7.4 g. (98%) of alight yellow oil.

EXAMPLE 70

Preparation of 2-(6-fluoro-6-carbethoxyhexyl)cyclopent-2-en-1-one

The acid ketone (7.4 g.) from Example 69 is Fisher esterified with 300ml. of absolute ethanol and 400 mg. of p-toluenesulfonic acid for 18hours, cooled, and the solvent is evaporated. The resulting oil isdissolved in ether, washed with dilute sodium bicarbonate solution, andsaline, dried (MgSO₄), and evaporated to give 7.306 g. (86%) of a lightyellow oil.

EXAMPLE 71 Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatmemnt of 1-methoximino-2-(7-p-toluenesulfonyloxy)-2-cyclopentene(Example 18) with sodium cyanide in the manner of Example 50 isproductive of the subject compound.

EXAMPLE 72 Preparation of2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene(Example 71) by the procedure of Example 51 is productive of the subjectcompound.

EXAMPLE 73 Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 72 with acetone-hydrochloric acidby the procedure of Example 52 is productive of the subject compound.

EXAMPLE 74 Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 73 by theprocedure of Example 53 is productive of the subject compound.

EXAMPLE 75

Preparation of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene(Example 60) with sodio diethyl phenylmalonate by the procedure ofExample 61 is productive of the subject compound.

EXAMPLE 76 Preparation of2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example75) by the procedure of Example 20 is productive of the subject diacid.

EXAMPLE 77 Preparation of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Decarboxylation of2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example76) by the procedure of Example 63 is productive of the subjectcompound.

EXAMPLE 78 Preparation of2-(6-carboxy-6-phenylhexyl)-2-cyclopentene-1-one

Methoxime cleavage of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 77) inthe manner of Example 69 is productive of the subject ketone.

EXAMPLE 79 Preparation of2-(6-carbethoxy-6-phenylhexyl)-2-cyclopenten-1-one

Fisher esterification of the carboxylic acid of Example 78 in the mannerof Example 70 is productive of the subject keto-ester.

EXAMPLE 80

Preparation of2-(6-fluoro-6,6-dicarbethocyhexyl)-1-methoximino-2-cyclopentene

An ethanolic solution of sodium ethoxide, prepared from 0.389 g. ofsodium and 40 ml. of absolute ethanol, is treated at ambienttemperatures with 5.05 g. of2-(6,6-dicarbethoxyhexyl)-1-methoximino-2-cyclopentene (Example 61). Theresulting solution is cooled to -20°C. and then treated with a stream ofperchloryl fluoride until the mixture becomes neutral. The excessperchloryl fluoride is removed with a stream of nitrogen and the mixtureis retreated with 10 ml. of an ethanolic solution of sodium ethoxide(from 0.350 g. of sodium) and then with perchloryl fluoride until themixture becomes neutral. The excess perchloryl fluoride is removed witha stream of nitrogen and the mixture is filtered and evaporated to anoil. The latter is partitioned between ether and water and the organicphase is washed with saturated saline, dried (Na₂ SO₄) and evaporated toafford the subject compound.

EXAMPLE 81 Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli etal., Tetrahedron Letters, No. 5, 465 (1966)] in 1400 ml. of n-butanolcontaining 2.7 g. of p-toluenesulfonic acid monohydrate is allowed tostand at room temperature in a stoppered flask for about 24 hours. Thesolution is taken to dryness. The residue is taken up in ether and theethereal solution is washed several times with saline solution, driedwith anhydrous magnesium sulfate, and taken to dryness to afford thesubject butyl ester.

EXAMPLES 82-84 Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one bythe procedure of Example 81 with the appropriate alcohol affords theesters of the following table.

                  TABLE IV                                                        ______________________________________                                        Ex.  Alcohol      Product Ester                                               ______________________________________                                        82   isopropanol                                                                              2-(6-carboisopropoxyhexyl)cyclopent-2-                                        en-1-one                                                      83   methanol   2-(6-carbomethoxyhexyl)cyclopent-2-en-                                        1-one                                                         84   1-hydroxy- 2-(6-carbo-n-decyloxyhexyl)cyclopent-                              n-decane   2-en-1-one                                                    ______________________________________                                    

EXAMPLE 85 Preparation of diethyl (5-chloro-1,1-dimethylpentyl)malonate

To magnesium (71 g. 2.92 moles) under 1 l. of ether containing a fewcrystals of iodine is added dropwise 1-chloro-4-bromobutane (500 g.,2.92 moles) over a period of 30 minutes with stirring under nitrogen.The reaction is maintained at a temperature of 0°C. to 5°C. by immersingin an acetone-Dry Ice bath periodically. After stirring for 30 minutesat room temperature, the solution is chilled to below 0°C. and is thentransferred to a dropping funnel from which it is added dropwise todiethyl isopropylidene malonate (440 g., 2.19 moles) [A. C. Cope and E.M. Hancock, J.A.C.S. 60, 2644 (1938)] dissolved in 1000 ml. of ethercontaining the tri(n-butyl)phosphine complex of copper (I) iodide (57g.)[G. B. Kaufman and L. A. Teter, Inorganic Synthesis, 7, 9(1963)] at-10°C. with stirring under nitrogen over a period of two hours. Afterstirring at room temperature for four hours, the reaction mixture ispoured into cold dilute hydrochloric acid and is extracted with ether.The combined ether extracts are washed with saline solution, dried overmagnesium sulfate, and concentrated in vacuo to give 700 g. of crudeamber oil, which is distilled under vacuum to yield two fractions: 212.4g. with b.p. at 110°-135°C. at 0.3 mm. and 100.0 g. with b.p. at135°-145°C. at 0.3 mm. The total yield is 312.4 g. (49%).

EXAMPLE 86 Preparation of 3,3-dimethyl-7-chloroheptanoic acid

A mixture containing diethyl 5-(5-chloro-1,1-dimethylpentyl)malonate(648 g., 2.22 moles) potassium hydroxide (460 g.) and eight liters of1:1 isopropanol: water is stirred at room temperature overnight. Most ofthe isopropanol is distilled and the residue is diluted with water, andthen carefully acidified with conc. hydrochloric acid. The mixture isextracted with ether and the extracts are washed with water and saline,dried over magnesium sulfate and concentrated in vacuo to give 548 g. ofcrude oil. The oil is dissolved in 3 liters of diglyne which is heatedunder reflux for 16 hours. About 2.7 l. of solvent is distilled, and theremainder is diluted with water and extracted with ether. The extractsare washed with saline, dried over magnesium sulfate and concentrated invacuo to give 428 g. of crude oil (99%).

EXAMPLE 87 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3,3-dimethyl-7-chloroheptanoic acid (428 g., 2.21moles) in 3 l. of chloroform containing 3 ml. of N,N-dimethylformamideis added 500 ml. of thionyl chloride and the resulting solution istested under reflux for 3 hours. The reaction solution then isconcentrated in vacuo and the residual acid chloride is dissolved in aminimum amount of benzene and added slowly to a solution containing 1260ml. of 95% ethanol and 2520 ml. of benzene and 390 ml. of collidine.After heating under reflux for 1 hour, the solution is concentrated andthe residue is dissolved in ether washed with water, dilute sodiumbicarbonate solution and saline solution, dried over magnesium sulfateand concentrated to give 415 g. of crude oil, which is distilled undervacuum to yield two fractions: 46.6 g. boiling at 75°C. (0.3 mm.) and236.7 g. boiling at 75° - 80°C. (0.3 mm). The total yield is 283.3 g.(60%) and the product is indicated to be 95% pure by g.l.c.

EXAMPLE 88 Preparation of methyl/ethyl2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentanone-2-carboxylate

Sodium hydride (67 g., 1.55 moles) is placed in a three l. round-bottomflask and to this is added 1.1 liters of glyme from a dropping funnelunder nitrogen flow and with stirring. To the resulting grayish mixtureis added the 2-carbalkoxycyclopentanone (mixed methyl and ethyl esters)dropwise over a period of 45 minutes with nitrogen flow whilst thetemperature is maintained in the range of 40°-55°. Ethyl3,3-dimethyl-7-chloroheptanoate (283 g., 1.28 moles) and potassiumiodide (195 g., 1.32 moles) are added and the mixture is heated atreflux overnight. After most of the solvent is distilled, the residue ismade acidic with dilute hydrochloric acid and is then extracted withether. The ether extracts are washed with water and saline solution,dried over magnesium sulfate, and concentrated in vacuo to 500 g. ofcrude yellow oil, which is distilled to give 405 g. (94% yield) of oilwith b.p. 140°-180° (0.8 mm).

EXAMPLE 89 Preparation of 7-(2-Cyclopentanone)-3,3 dimethylheptanoicacid

Methyl/Ethyl 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentanone-2-carboxylate (200 g., 0.6 moles), glacial acetic acid(180 ml) and 240 ml. of diluted hydrochloric acid, prepared from 100 ml.of conc. hydrochloric acid and 300 ml. of water, are placed in a 2 l.flask, containing a reflux condenser and a magnetic stirrer. The mixturethen is stirred at reflux for 24 hours. The reaction mixture is cooled,1 l. of water is added and the mixture is extracted several times withbenzene. The organic extracts are combined, washed with saturated sodiumchloride solution, dried over magnesium sulfate, filtered andconcentrated to an oil (173.5 g.). The oil is rendered basic with sodiumhydroxide solution, extracted with benzene and made acidic withhydrochloric acid and reextracted with benzene several times. Thebenzene layers are combined and washed with water, saturated sodiumchloride solution, dried over magnesium sulfate, filtered andconcentrated to yield 109.8 g. (78%) of crude oil, which was usedwithout further purification in the next step.

EXAMPLE 90 Preparation of Ethyl7-(2-Cyclopentanone)-3,3-dimethylheptanoate

To a solution of 7-(2-cyclopentanone)-3,3-dimethylheptanoic acid (45 g.,0.22 mol.) in 285 ml. of chloroform containing three drops ofN,N-dimethylformamide is added dropwise 25 ml. of thionyl chloride. Thesolution is stirred at room temperature for twenty minutes, the solventis removed at reduced pressure and the resudual acid chloride isdissolved in a minimum amount of benzene and added slowly to a solutioncontaining 115 ml. of ethanol, 230 ml. benzene and 30 ml. of collodine.This solution is heated under reflux for fifteen minutes and thenconcentrated. The residue is dissolved in ether, washed with water,diluted sodium bicarbonate solution and saline solution, dried overmagnesium sulfate and concentrated to give 51 g. of crude oil.Distillation gives 40 g. (67%) b.p. 135°-145° (0.1 mm.) of oil.

EXAMPLE 91 Preparation of1-Acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

A solution of ethyl 7-(2-cyclopentanone)-3,3-dimethylheptanoate (90 g.,0.336 mol.) and p-toluenesulfonic acid (0.94 g.) in 250 ml. of aceticanhydride is heated to boiling under partial reflux, allowing distillateat 118° or less (i.e. acetic acid) to escape thru a Vigruex columnequipped with a condenser to collect the distillate. After ten hours 130ml. of distillate is collected. Another 50 ml. of acetic anhydride isadded and the reactor heated for five more hours; an additional 125 ml.of acetic anhydride is added, the reaction is heated for seven morehours; finally another 50 ml. of acetic anhydride is added and heatingis continued for 4 more hours. The solution is cooled and poured(cautiously) into a cold (0°-5°) mixture of saturated aqueous sodiumbicarbonate (400 ml.) and hexane (250 ml.). The resulting cold mixtureis stirred for 30 minutes during which time portions of solid sodiumbicarbonate are added periodically until carbon dioxide evalutionceases. The hexane layer is separated and washed with saturated sodiumchloride solution until the washings are neutral, dried over magnesiumsulfate and treated with Darco decolorizing charcoal for clarificationand then evapoated to dryness leaving an amber colored oil (87.5 g.,84%).

EXAMPLE 92 Preparation of2-(6-Carboxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene (35 g.,0.113 mole) chloroform (95 ml.), water (125 ml.) and calcium carbonate(11.8 g.) cooled in an ice-bath is added dropwise over a period ofthirty minutes a solution of bromine (18.8 g) in carbon tetrachloride(31 ml.). After stirring in the cold for an additional 45 minutes theorange colored chloroform layer is separated and washed with dilutesodium bisulfite and saturated saline solution dried over magnesiumsulfate and taken to dryness in vacuo (bath temperature: 35°-40°)leaving an amber colored oil. A slurry of 100 ml. ofN,N-dimethylacetamide and 16.5 g. of CaCO₃ is stirred and heated toreflux under nitrogen flow. The above dried oil is added from a droppingfunnel rapidly, maintaining reflux and nitrogen flow for 30 minutes. Thecooled reaction mixture is filtered, and the precipitate is washed withether. The filtrate is poured into two liters ice-cold water and isextracted with ether. The combined extracts and washing is washed withwater, saturated saline, treated with decolorizing charcoal, filtered.The solvent evaporated in vacuo to give 24 g. (77%) of subject product.

EXAMPLE 93 Preparation of 4-bromo-2(6-carboxyhexyl)cyclopent-2-en-1-one

A stirred mixture of 35.9 g. (0.171 moles) of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465(1966)], 35.0 g. (0.197 moles) of N-bromosuccinimide, and 600 ml. ofcarbon tetrachloride is refluxed for 35 minutes. The mixture is cooledto 5°C. and filtered. The filtrate is washed with cold water, dried overmagnesium sulfate, and taken to dryness to give an oil, λ_(max).^(MeOh)= 225 mμ (8850); νmax. = 1705 (carbonyl groups) and 1625. cm⁻ ¹ (olefingroup).

EXAMPLE 94 Preparation of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one

To a stirred solution of 10.6 g. (ca. 34 mmoles) of crude4-bromo-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 93) in 100 ml.of acetone and 65 ml. of water is added 8.80 g. (45.2 mmoles) of silverfluoborate during 2 minutes. The temperature is maintained at 25°-30°C.by external cooling. The mixture is stirred for 90 minutes, filtered,saturated with sodium chloride, and extracted with ether. The extract isextracted with half saturated sodium bicarbonate solutions. The basicsolutions is reacidified with dilute hydrochloric acid, saturated withsodium chloride, and extracted with ether. The extract is washed withwater and saturated sodium chloride solution, dried over magnesiumsulfate, and concentrated. The crude product is purified by partitionchromatography on Celite to give an oil; λ_(max)..sup. MeOH = 233 mμ.(7360); νmax. = 3380 (hydroxyl groups), 1710 (carbonyl groups), and 1632cm⁻ ¹ (olefin group).

EXAMPLE 95 Preparation of4-tetrahydropyranyloxy-2-(6-tetrahydropyranylcarboxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 5.59 g. (24.6 mmoles) of4-hydroxy-2-(6-carboxyhexyl) cyclopent-2-en-1-one (Example 94) and 20.7g. (246 mmoles) of dihydropyran in 100 ml. of methylene chloride at20°C. is added 47 mg. (0.246 mmoles) of p-toluenesulfonic acidmonohydrate in one portion. The temperature is maintained at 20°-25°C.by cooling and is stirred for one hour at that temperature. The solutionis diluted with 200 ml. of ether and poured into a mixture of 40 ml. ofsaturated sodium bicarbonate solution, 40 ml. of saturated sodiumchloride solution, and 80 ml. of water. The phases are separated, andthe aqueous phase is extracted with additional ether. The total extractis washed successively with water and saturated sodium chloridesolution, dried over potassium carbonate, and freed of volatile matterby concentration at reduced pressure to give an oil, λ_(max).^(MeOH) =223 mμ (9500); νmax. 1730 (ester carbonyl group), 1705 (ketone carbonylgroup), and 1030 cm⁻ ¹ (tetrahydropyranyloxy groups).

EXAMPLE 96 Preparation of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenonemethoxime

The subject compound is prepared from sodio diethyl methylmalonate and2-(5-methanesulfonyloxypentyl)-2-cyclopentenone methoxime (Example 60)by the procedure described in Example 61.

EXAMPLE 97 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime

Saponification of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime(Example 96) with potassium hydroxide by the method of Example 20 isproductive of 2-(6,6-dicarboxyheptyl)-2-cyclopentenone methoxime,decarboxylation of which in the manner of Example 63 provides thesubject compound.

EXAMPLE 98 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone

Methoxime cleavage of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime(Example 97) in the manner of Example 22 provides the subject ketone.

EXAMPLE 99 Preparation of 2-(6-carbethoxyheptyl)-2-cyclopentenone

Esterification with ethanol of the acid chloride derived from2-(6-carboxyheptyl)-2-cyclopentenone in the manner of Example 31 isproductive of the subject compound.

EXAMPLE 100 Preparation of ethyl (methyl)7(2-carbethoxycyclohexan-1-on-2-yl)heptanoate

To a stirred suspension of 51 g. of sodium hydride (57% in mineral oil)in 675 ml. of dimethylformamide is added 200 g. of 2-cyclohexanonecarboxylate (60% ethyl - 40% methyl esters) over a 1-5 hr. period withexternal cooling to mantain the temperature at 20°-25°C. The reactionmixture is stirred at ambient temperature for 15 minutes and heated to50°C. over 15 minutes. To a stirred mixture is added 300 g. of ethyl7-bromoheptanoate during a 10 minute period. The reaction mixture isstirred at 50°-60°C. for 4 hours, cooled, and poured into water. Theproduct is obtained by ether extraction. The extract is washedsuccessively with water and saturated sodium chloride, dried andevaporated to give a liquid which is purified by distillation, IR 1735cm⁻ ¹ (ester carbonyls) and 1710 cm⁻ ¹ (ketone carbonyl).

EXAMPLE 101 Preparation of 7-(cyclohexan-1-on- 2-yl)heptanoic acid

A stirred mixture of 380 g. of mixed methyl and ethyl esters of7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate (Example 10), 202 ml. ofconcentrated sulfuric acid, 970 ml. of glacial acetic acid, and 970 ml.of water is refluxed for 22.5 hours. The cooled reaction mixture istreated with 380 g. of sodium carbonate and 2 liters of water and isextracted with ether. Acidic material is partitioned from the etherextract with 1.0M sodium carbonate. The aqueous phase is acidified withconcentrated hydrochloric acid and extracted with ether. The extract iswashed successively with water and saturated sodium chloride, dried, andevaporated to give an oil.

EXAMPLE 102 Preparation of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate

A solution of 232 g. of 7-(cyclohexan-1-on-2-yl)heptanoic acid in 2500ml. of ethanol is refluxed for 4.5 hours with 3.8 g. ofp-toluenesulfonic acid monohydrate. The solution is diluted with 200 ml.of benzene, and boiling is continued for 2 hours as 200 ml. ofdistillate is removed. The volume of the solution is concentrated to 500ml. After dilution with 500 ml. of ether the solution is extracted witha solution prepared from 50 ml. of saturated sodium bicarbonate, 50 ml.of saturated sodium chloride, and 100 ml. of water. The extract iswashed with saturated sodium chloride, dried, and evaporated. Theproduct is purified by distillation to give a liquid, IR 1740 cm⁻ ¹(ester carbonyl) and 1715 cm⁻ ¹ (ketone carbonyl).

EXAMPLE 103 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one

The subject compound is prepared in the manner described in Example 10by treatment of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with sodium hydride and ethyl 4-iodobutyrate.

EXAMPLE 104 Preparation of 2-(3-carbethoxypropyl)cyclohexan-1-one

This compound is prepared from2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one(Example 13) by decarbalkoxylation according to the procedure describedin Example 11 followed by esterification by the procedure of Example 12.

EXAMPLE 105 Preparation of 2-(5-carbethoxypentyl)cyclohexan-1-one

This compound is prepared by alkylation of 2-cyclohexanone carboxylate(mixed methyl and ethyl esters) with ethyl 6-bromohexanoate according tothe procedure of Example 10, followed by decarbalkoxylation according tothe procedure of Example 11 and finally esterification by the procedureof Example 12.

EXAMPLE 106 Preparation of 2-(7-carbethoxyheptylcyclonhexan-1-one

Alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with ethyl 8-bromoctanoate in accordance with the procedure ofExample 10, followed by decarbalkoxylation by the procedure of Example11 and then esterification by the procedure of Example 12 is productiveof the subject compound.

EXAMPLE 107 Preparation of ethyl7-(1-acetoxycyclohex-1-en-2-yl)heptanoate

A stirred solution of 28.0 g. of ethyl 7-(cyclohexan-1-on-2yl)heptanoate(Example 12), 170 mg. of p-toluenesulfonic acid monohydrate, and 25.6 g.of acetic anhydride is heated for 5 hours while allowing 8.0 g. ofdistillate to distill. The cooled solution is poured into a stirred,ice-cold mixture of 500 ml. of saturated sodium bicarbonate and 250 ml.of hexane. After one hour the hexane phase is separated, dried, andevaporated. The crude product is distilled to give a liquid, IR 1760 cm⁻¹ (vinyl ester carbonyl) and 1740 cm⁻ ¹ (ethyl ester carbonyl).

EXAMPLE 108 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene

Treatment of 2-(3-carbethoxypropyl)cyclohexan-1-one (Example 14) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 109 Preparation of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene

Treatment of 2-(5-carbethoxypentyl)cyclohexan-1-one (Example 15) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 110 Preparation of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene

Treatment of 2-(7-carbethoxyheptyl)cyclohexan-1-one (Example 16) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 111 Preparation of ethyl 7-(cyclohex-2-en-1-one- 2-yl)heptanoate

To a stirred solution of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate(Example 24) in 750 ml. of acetic acid and 125 ml. of pyridine at 10°C.is added a solution of 13.8 g. of bromine in 200 ml. of acetic acid over20 minutes. The resulting solution is allowed to stand at ambienttemperature for 45 minutes and is then decolorized with sodium sulfite.The solution is poured into 800 ml. of half-saturated sodium chlorideand extracted with 1:1 hexane-ether. The extract is washed successivelywith water and saturated sodium chloride, dried over sodium carbonate,and evaporated to give 32 g. of the crude bromoketone. To a stirredsuspension of 14.2 g. of lithium bromide and 16.6 g. of lithiumcarbonate in 250 ml. of anhydrous dimethylformamide at 80°C. is addedthe above bromoketone. The stirred mixture is heated to boiling over 20minutes and refluxed for 15 minutes. The cooled mixture is poured into1000 ml. of water, acidified with dilute hydrochloric acid, andextracted with ether. The extract is washed successively with water andsaturated sodium chloride, dried, and evaporated. The product ispurified by distillation to give a liquid, IR 1740 cm⁻ ¹ (estercarbonyl), 1685 cm⁻ ¹ (ketone carbonyl), and 1650 cm⁻ ¹ (olefin); NMR(CCl₄) 6.63 (multiplet, vinyl proton).

EXAMPLE 112 Preparation of 2-(3-carbethoxypropyl)cyclohex-2-en-1-one

In accordance with the procedure of Example 40, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1ene (Example 25) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 113 Preparation of 2-(5-carbethoxypentyl)cyclohex-2-en-1-one

By the procedure of Example 40, bromination of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1 -ene (Example 26) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 114 Preparation of 2-(7-carbethoxyheptyl)cyclohex-1-en-2-one

By the procedure of Example 40, bromination of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene (Example 27) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 115 Preparation of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene

In the manner described in Example 34, treatment of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene with p-toluene sulfonylchloride in pyridine gives the subject product as a light yellow oil; IR(film): 1600, 1190, 1050, 885 cm⁻ ¹.

EXAMPLE 116 Preparation of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene

To a stirred mixture of 1.465 g. (0.0348 mole) of sodium hydride (57.2%in mineral oil) in 50 ml. of dimethoxyethane, under nitrogen, is addedslowly 4.8 g. (0.0347 mole) of ethyl-2-mercaptoacetate. The reactionmixture is stirred at room temperature for one hour and then a solutionof 7.8 g. (0.0231 mole of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene in 30 ml.of dimethoxyethane is added dropwise and stirred at room temperature for18 hours. The solution is heated at reflux for one hour, cooled andpoured into cold dilute hydrochloric acid and then extracted with ether.The combined ether extracts are washed with saline, dried over magnesiumsulfate and evaporated to give 7.6 g. of subject product as a yellowoil.

EXAMPLE 117 Preparation of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 38, treatment of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene with acetoneand 2N hydrochloric acid at reflux gives the subject product as a yellowoil.

EXAMPLE 118 Preparation of 2-(6-carbethoxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 39, treatment of2-(6-carboxy-5-thiahexyl)-2-cyclopentenone with p-toluenesulfonic acidin ethanol gives the subject ester as a yellow oil.

EXAMPLE 119 Preparation of 3-triphenylmethoxy-1-octyne

A mixture of 1.26 g. (10.0 mmoles) of 1-octyn-3-ol, 4.85 g, (15.0mmoles) of triphenylmethyl bromide, and 50 ml. of dry pyridine is heatedat 95°C. for 60 minutes with occasional swirling. The solution iscooled, treated with water, and extracted with ether. The extract iswashed successively with water and saturated sodium chloride solution,dried over magnesium sulfate, and concentrated. The crude product ispurified by chromatography on Florisil and rectystallization frompetroleum ether to give white crystals, m.p. 65°-66.5°, μ max. (KBr)3280 (acetylenic hydrogen), 1605, 1030, and 702 cm⁻ ¹ (triphenylmethoxygroup).

EXAMPLE 120 Preparation of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate

A stirred solution of 7.37 g. (20.0 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of benzene istreated with 16.7 mg. of 1.2 M diisobutylaluminum hydride in hexane, andthe resulting solution is heated at 50°C. for 2 hours. The solution iscooled to 0°C. and treated with 10.5 ml. of 1.7 M methyl lithium inether. After stirring for a 20 minute period at ambient temperature, thealanate solution is cooled to 0°C. and treated with a solution of 3.98g. (16.7 mmoles) of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example13) in 5 ml. of ether. The resulting solution is stirred at ambienttemperature for 22.5 hours, diluted with ether, and poured into astirred mixture 2N acetic acid and ice. After stirring until methaneevolution ceases, the organic phase is separated and washed successivelywith water and saturated sodium chloride solution. The extract is driedover magnesium sulfate and concentrated. The crude product in theresidue is purified by chromatography on silica gel to give an oil, νmax. 1735 (carbonyl groups), 967 (trans vinyl group), and 705 cm⁻ ¹(triphenylmethoxy group).

EXAMPLE 121 Preparation of ethyl 15-hydroxy-9-oxo-13 -trans-prostenoate

A 0.05M solution of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate (Example 120) inglacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45°C. for3.5 hours. The solvents are evaporated at reduced pressure, and theresidue is dissolved in ether. The solution is washed successively withwater, 0.5N sodium bicarbonate solution, and saturated sodium chloridesolution; dried over magnesium sulfate; and concentrated. Columnchromatography of the crude product on silica gel gives two epimericsubstances which are purified separately by thin layer chromatography togive oils differing only in chromatographic behavior, ν max. 3470(hydroxyl group), 1735 (carbonyl groups), and 967 cm⁻ ¹ (trans vinylgroup).

EXAMPLE 122 Preparation of 15-hydroxy-9-oxo-13-trans-prostenoic acid

A solution of 2 g. of ethyl 15-hydroxy-9-oxo-13,14-trans-prostenoate(Example 121) (mixture of racemates) in 32 ml. of methanol-water (1:1),containing 850 mg. of potassium hydroxide is stirred at ambienttemperature for 18 hours. After acidification with 10% hydrochloricacid, the solution is extracted with ether several times. The combinedether extracts are washed with saturated sodium chloride solution, driedwith anhydrous magnesium sulfate and taken to dryness to give 1.69 g.(92%) of an oil which partially crystallizes. Recrystallized fromether-hexane gives white crystals, m.p. 79°-81°C.; nmr δ 6.36 (s,hydroxyl and carboxyl groups), 5.61 (t, olefinic protons), 4.12 (s, C₁₅-H) and 0.90 (s, terminal methyl).

EXAMPLE 123 Preparation of tetrahydropyran-2-yl9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-8ξ-prostenoate

In the manner described in Example 120, 13.6 g. (37 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) contained in 18.5 ml. ofbenzene is converted to an alanate reagent by treatment with 31 ml. of1-2M diisobutylaluminum hydride in hexane and 21 ml. of 1.7M methyllithium in ether. To the stirred, ice-cold reagent is added a solutionof 10.97 g. (24.6 mmoles) of2-(6-tetrahydropyranylcarboxylhexyl)-4-tetrahydropyranyloxycyclopent-2-en-1-one(Example 95) in 10 ml. of ether during 10 minutes. The resultingsolution is stirred at ambient temperature for 20 hours, diluted withether, and poured into a stirred mixture of 2N hydrochloric acid andice. The organic phase is separated and washed successively with waterand saturated sodium chloride solution. The extract is dried overmagnesium sulfate, and the solvents are evaporated at reduced pressureto give the crude product as an oil, ν max. 1735 (carbonyl groups), 1030(tetrahydropyranyloxy groups), 970 (trans vinyl group), and 705 cm⁻ ¹(triphenylmethoxy group).

EXAMPLE 124 Preparation of 11,15-dihydroxy-9-oxo-13-trans-prostenoicacids

A 0.05M solution of crude tetrahydropyran-2-yl9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-prostenoate(Example 123) in glacial acetic acid-tetrahydrofuran-water (4:2:1) isheated at 45°C. for 3.5 hours. The solution is diluted with water andextracted with ether. The extract is washed successively with water andsaturated sodium chloride solution and dried over magnesium sulfate. Thesolvents are removed at reduced pressure. Column chromatography of theresidue on acid-washed silica gel gives the title compounds as a pair ofepimeric substances which are purified separately by partitionchromatography.

The fast-running epimer (15-epi-d,1-prostaglandin E₁) is obtained as anoil, ν max. 1735 (ketone carbonyl group), 1710 (acid carbonyl group),and 967 cm⁻ ¹ (trans vinyl group); NMR (acetone-d₆) 5.68 (multiplet,vinyl hydrogens) and 4.11 ξ (multiplet, carbinolic hydrogens).

The slow-running epimer (d,1-prostaglandin E₁) is recrystallized fromethyl acetate-petroleum ether to give white crystals, m.p. 100°-105°C.,ν max. (KBr) 1725 (ketone carbonyl group), 1700 (acid carbonyl group),and 970 cm⁻ ¹ (trans vinyl group); NMR (acetone-d₆) 5.67 (multiplet,vinyl hydrogens) and 4.12 (multiplet, carbinolic hydrogens).

EXAMPLES 125 TO 139

In accordance with the method described in Example 119, the various3-hydroxy-1-alkynes listed in the table below are converted to thecorresponding 3-triphenylmethoxy-1-alkynes by treatment withtriphenylmethyl bromide.

                                      TABLE                                       __________________________________________________________________________    125  1-heptyn-3-ol  3-triphenylmethoxyheptyne-1                               126  1-hexyn-3-ol   3-triphenylmethoxy-hexyne-1                               127  1-pentyn-3-ol  3-triphenylmethoxy-pentyne-1                              128  1-nonyne-3-ol.sup.a                                                                          3-triphenylmethoxy-nonyne-1                               129  1-decyne-3-ol.sup.b                                                                          3-triphenylmethoxy-decyne-1                               130  4-ethyl-1-octyne-3-ol                                                                        3-triphenylmethoxy-4-ethyl-                                                   octyne-1                                                  131  4-ethyl-1-hexyne-3-ol                                                                        3-triphenylmethoxy-4-ethyl-                                                   hexyne-1                                                  132  4-methyl-1-heptyne-3-ol                                                                      3-triphenylmethoxy-4-methyl-                                                  heptyne-1                                                 133  4-methyl-1-pentyne-3-ol                                                                      3-triphenylmethoxy-4-methyl-                                                  pentyne-1                                                 134  7-methyl-6-en-1-octyne-                                                                      3-triphenylmethoxy-7-methyl-                                   3-ol.sup.c     6-en-octyne-1                                             135  6,7-dimethyl-6-en-1-                                                                         3-triphenylmethoxy-6,7-                                        octyne-3-ol.sup.c                                                                            dimethyl-6-en-octyne-1                                    136  7-isobutyl-6-en-1-                                                                           3-triphenylmethoxy-7-isobutyl-                                 octyne-3-ol.sup.c                                                                            6-en-octyne-1                                             137  5-en-1-hexyne-3-ol.sup.d                                                                     3-triphenylmethoxy-5-en-                                                      hexyne-1                                                  138  5,9-dimethyl-9-en-1-                                                                         3-triphenylmethoxy-5,9-                                        decyne-3-ol.sup.e                                                                            dimethyl-9-en-decyne-1                                    139  cis-5-en-1-octyne-3-                                                                         3-triphenylmethoxy-cis-5-en-                                   ol.sup.f       octyne-1                                                  __________________________________________________________________________     References:                                                                   .sup.a M. Bertrand, Bull. Soc. Chim. France, 461 (1956).                      .sup.b F. Bohlmann and D. Ratz, Chem. Ber., 90, 2265 (1957).                  .sup.c U.S. Pat. No. 3,452,105 (June 24, 1969); Chem. Abs., 71, 60678         (1969).                                                                       .sup.d A. Viola and J. H. MacMillan, Jour. Amer. Chem. Soc., 92, 2404         (1970).                                                                       .sup.e Sequin, Bull. Soc. Chim. France, 12, 948 (1945).                       .sup.f J. Fried et al., Jour. Amer. Chem. Soc., 94, 4342 (1972).         

EXAMPLES 140-256

Treatment of the cycloalkenone designated in the table below with thealanate [lithiumdiisobutyl-methyl-(3-triphenylmethoxy-1-trans-alkenyl)-alanate] preparedby treatment of the listed 3-triphenylmethoxy-1-alkyne with diisobutylaluminum hydride followed with methyl lithium, all by the proceduredescribed in Example 120, is productive9-oxo-15-triphenylmethoxy-13-trans-8-ξ -prostenoates of the table.

                                      Table 3                                     __________________________________________________________________________                       Starting 3-triphenyl-                                                                       Product                                           Starting Cycloalkenone                                                                      methoxy-1-alkyne of                                                                         Alkyl 9-oxo-15-triphenylmethoxy-13-trans-                                     3                                            Example                                                                            of Example    Example       8ξ -prostenoate                           __________________________________________________________________________    140  14            119           ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri                                     -                                                                             nor-13-trans-8ξ-prostenoate               141  23            119           ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis                                     -                                                                             homo-13-trans-8ξ-prostenoate              142  31            119           ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-1                                     3-                                                                            trans-8ξ-prostenoate                      143  41            119           ethyl 9-oxo-15-triphenylmethoxy-3,3-dimet                                     hyl-                                                                          13-trans-8ξ-prostenoate                   144  46            119           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-13-                                     trans-8ξ-prostenoate                      145  53            119           ethyl 9-oxo-15-triphenylmethoxy-7-nor-13-                                     trans-8ξ-prostenoate                      146  70            119           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     13-                                                                           trans-8ξ-prostenoate                      147  74            119           ethyl 9-oxo-15-triphenylmethoxy-7a-homo-1                                     3-                                                                            13-trans-8ξ-prostenoate                   148  79            119           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     13-                                                                           trans-8ξ-prostenoate                      149  99            119           ethyl 9-oxo-15-triphenylmethoxy-2-methyl-                                     13-                                                                           trans-8ξ-prostenaoate                     150  111           119           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     13-                                                                           trans-8ξ-prostenoate                      151  112           119           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     5,-                                                                           6,7-trinor-13-trans-8ξprostenoate         152  113           119           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     7-                                                                            nor-13-trans-8ξ-prostenoate               153  114           119           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     s-                                                                            homo-13-trans-8ξ-prostenoate              154  118           119           ethyl 9-oxo-15-triphenylmethoxy-3-thia-13                                     -                                                                             13-trans-8ξ-prostenoate                   155  81            119           butyl 9-oxo-15-triphenylmethoxy-13-trans-                                     8ξ-                                                                        prostenoate                                  156  82            119           isopropyl 9-oxo-15-triphenylmethoxy-13-tr                                     ans-                                                                          8ξ-prostenoate                            157  83            119           methyl 9-oxo-15-triphenylmethoxy-13-trans                                     -8ξ-                                                                       prostenoate                                  158  84            119           n-decyl 9-oxo-15-triphenylmethoxy-13-tran                                     s-                                                                            8ξ-prostenoate                            159  900           119           methyl 9-oxo-15-triphenylmethoxy-5-cis,13                                     -                                                                             trans-8ξ-prostadienoate                   160  13            125           ethyl 9-oxo-15-triphenylmethoxy-20-nor-13                                     -                                                                             trans-8ξ-prostenoate                      161  13            128           ethyl 9-oxo-15-triphenylmethoxy-20-methyl                                     -                                                                             13-trans-8ξ-prostenoate                   162  13            130           ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-                                     13-                                                                           trans-8ξ-prostenoate                      163  13            132           ethyl 9-oxo-15-triphenylmethoxy-16-methyl                                     -20-                                                                          nor-13-trans-8ξ-prostenoate               164  13            134           ethyl 9-oxo-15-triphenylmethoxy-19-methyl                                     -13-                                                                          trans,18-8ξ-prostadienoate                165  13            135           ethyl 9-oxo-15-triphenylmethoxy-18,19-di-                                     methyl-13-trans,18-8ξ-prostadienoate      166  13            139           ethyl 9-oxo-15-triphenylmethoxy-8ξ-13-                                     trans,                                                                        17-cis-prostadienoate                        167  14            139           ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri                                     nor-                                                                          8ξ-13-trans,17-cis-prostadienoate         168  15            139           ethyl 9-oxo-15-triphenylmethoxy-6,7-dinor                                     -8ξ-                                                                       13-trans,17-cis-prostadienoate               169  23            139           ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis                                     homo-                                                                         8ξ-13-trans,17-cis-prostadienoate         170  31            139           ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-8                                     ξ-13-                                                                      trans,17-cis-prostadienoate                  171  41            139           ethyl 9-oxo-15-triphenylmethoxy-3,3-dimet                                     hyl-                                                                          8ξ-13-trans,17-cis-prostadienoate         172  46            139           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-8.x                                     i.-13-                                                                        trans,17-cis-prostadienoate                  173  53            139           ethyl 9-oxo-15-triphenylmethoxy-7-nor-8.x                                     i.-13-                                                                        trans,17-cis-prostadienoate                  174  70            139           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     8ξ-13-                                                                     trans,17-cis-prostadienoate                  175  74            139           ethyl 9-oxo-15-triphenylmethoxy-7a-homo-8                                     ξ-13-                                                                      trans,17-cis-prostadienoate                  176  79            139           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     8ξ -13-                                                                    trans,17-cis-prostadienoate                  177  99            139           ethyl 9-oxo-15-triphenylmethoxy-2-methyl-                                     8ξ-13-                                                                     trans,17-cis-prostadienoate                  178  111           139           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     8ξ-13-                                                                     trans,17-cis-prostadienoate                  179  112           139           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     5,6,7-                                                                        trinor-13-trans, 17-cis-prostadienoate       180  113           139           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     7-nor-                                                                        8ξ-13-trans,17-cis-prostadienoate         181  114           139           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     shomo-                                                                        8ξ-13-trans,17-cis-prostadienoate         182  118           139           ethyl 9-oxo-15-triphenylmethoxy-3-thia-8.                                     xi.-13-                                                                       trans,17-cis-prostadienoate                  183  81            139           butyl 9-oxo-15-triphenylmethoxy-8ξ-13-                                     trans,17-                                                                     cis-prostadienoate                           184  82            139           isopropyl 9-oxo-15-triphenylmethoxy-8ξ                                     -13-trans,                                                                    cis-prostadienoate                           185  83            139           methyl 9-oxo-15-triphenylmethoxy-8ξ-13                                     -trans,                                                                       17-cis-prostadienoate                        186  84            139           n-decyl 9-oxo-15-triphenylmethoxy-8ξ-1                                     3-trans,17-                                                                   cis-prostadienoate                           187  14            136           ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri                                     nor-19-                                                                       isobutyl-8ξ-13-trans,18-prostadienoate    188  14            137           ethyl 9-oxo-15-triphenylmethoxy-5,6,7,19,                                     20-penta-                                                                     nor-8ξ-13-trans-17,prostadienoate         189  13            137           ethyl 9-oxo-15-triphenylmethoxy-19,20-din                                     or-8ξ-13-                                                                  trans,18-prostadienoate                      190  13            138           ethyl 9-oxo-15-triphenylmethoxy-17-methyl                                     -20-iso-                                                                      propenyl-8ξ-trans-prostenoate             191  15            131           ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-                                     6,7,19,                                                                       20-tetranor-8ξ-13-trans-prostenoate       192  15            135           ethyl 9-oxo-15-triphenylmethoxy-18,19-dim                                     ethyl-6,                                                                      7-dinor-8ξ-13-trans,18-prostadienate      193  23            130           ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-                                     7a,7b-                                                                        bishomo-8ξ-13-trans-prostenoate           194  23            134           ethyl 9-oxo-15-triphenylmethoxy-19-methyl                                     -7a,7b-                                                                       bishomo-8ξ-13-trans,18-prostadienoate     195  31            126           ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-1                                     9,20-                                                                         dinor-8ξ-13-trans-prostenoate             196  31            129           ethyl 9-oxo-15-triphenylmethoxy-2,20-diet                                     hyl-                                                                          8ξ-13-trans-prostenoate                   197  31            132           ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-1                                     6-                                                                            methyl-8ξ-20-nor-13-trans-prostenoate     198  31            135           ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-1                                     8,                                                                            19-dimethyl-8ξ-13-trans,18-prostadieno                                     ate                                          199  41            127           ethyl 9-oxo-15-triphenylmethoxy-3,3-dimet                                     hyl-                                                                          18,19,20-trinor-8ξ-13-trans-prostenoat                                     e                                            200  41            128           ethyl 9-oxo-15-triphenylmethoxy-3,3,20-tr                                     i-                                                                            methyl-8ξ-13-trans-prostenoate            201  41            132           ethyl 9-oxo-15-triphenylmethoxy-3,3,16-tr                                     i-                                                                            methyl-20-nor-8ξ-13-trans-prostenoate     202  41            136           ethyl 9-oxo-15-triphenylmethoxy-3,3-dimet                                     hyl-                                                                          19-isobutyl-8ξ-13-trans,18-prostadieno                                     ate                                          203  41            137           ethyl 9-oxo-15-triphenylmethoxy-3,3-dimet                                     hyl-                                                                          19,20-dinor-8ξ-3-trans,17-prostadienoa                                     te                                           204  46            125           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-                                     nor-                                                                          8ξ-13-trans-prostenoate                   205  46            128           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-                                     methyl-8ξ-13-trans-prostenoate            206  46            130           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     ethyl-8ξ-13-trans-prostenoate             207  46            132           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     methyl-20-nor-8ξ-13-trans-prostenoate     208  46            137           ethyl 9-oxo-15-triphenylmethoxy-3-oxa-19,                                     20-                                                                           dinor-8ξ-13-trans,17-prostadienoate       209  53            137           ethyl 9-oxo-15-triphenylmethoxy-7,19,20-t                                     ri                                                                            nor-8ξ-13-trans,17-prostadienoate         210  53            135           ethyl 9-oxo-15-triphenylmethoxy-7-nor-18,                                     19-                                                                           dimethyl-8ξ-13-trans,18-prostadienoate    211  53            133           ethyl 9-oxo-15-triphenylmethoxy-7,18,19,2                                     0-                                                                            tetranor-16-methyl-8ξ-13-trans-prosten                                     oate                                         212  70            125           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     20-                                                                           nor-8ξ-13-trans-prostenoate               213  70            129           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     20-                                                                           ethyl-8ξ-13-trans-prostenoate             214  70            131           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     16-                                                                           ethyl-19,20-dinor-8ξ-13-trans-prosteno                                     ate                                          215  70            132           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     16-                                                                           methyl-20-nor-8ξ-13-trans-prostenoate     216  70            134           ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-                                     19-                                                                           methyl-8ξ-13-trans,18-prostadienoate      217  74            135           ethyl 9-oxo-15-triphenylmethoxy-7a-homo-1                                     8,19-                                                                         dimethyl-8ξ-13-trans,18-prostadienoate                                     N                                            218  74            137           ethyl 9-oxo-15-triphenylmethoxy-7a-homo-1                                     9,20-                                                                         dinor-8ξ-13-trans,17-prostadienoate       219  79            125           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     20-                                                                           nor-8ξ-13-trans-prostenoate               220  79            129           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     20-                                                                           ethyl-8ξ-13-trans-prostenoate             221  79            130           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     16-                                                                           ethyl-8ξ-13-trans-prostenoate             222  79            133           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     16-                                                                           methyl-18,19,20-trinor-8ξ-trans-proste                                     noate                                        223  79            135           ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-                                     18,                                                                           19,-dimethyl-8ξ-13-trans,18-prostadien                                     oate                                         224  99            125           ethyl 9-oxo-15-triphenylmethoxy-2-methyl-                                     20-                                                                           nor-8ξ-13-trans-prostenoate               225  99            128           ethyl 9-oxo-15-triphenylmethoxy-2,20-dime                                     thyl-                                                                         8ξ-13-trans-prostenoate                   226  99            131           ethyl 9-oxo-15-triphenylmethoxy-2-methyl-                                     16-                                                                           ethyl-19,20-dinor-8ξ-13-trans-prosteno                                     ate                                          227  99            134           ethyl 9-oxo-15-triphenylmethoxy-2,19-dime                                     thyl-                                                                         8ξ-13-trans,18-prostadienoate             228  99            137           ethyl 9-oxo-15-triphenylmethoxy-2-methyl-                                     19,                                                                           20-dinor-8ξ-13-trans,17-prostadienoate    229  111           125           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     20-                                                                           nor-8ξ-13-trans-prostenoate               230  111           128           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     20-                                                                           methyl-8ξ-13-trans-prostenoate            231  111           130           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     16-                                                                           ethyl-8ξ-13-trans-prostenoate             232  111           135           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     18, -   19-dimethyl-8ξ-13-trans,18-pro                                     stadienoate                                  233  111           137           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     19,                                                                           20-dinor-8ξ-13-trans,17-prostadienoate                                     T                                            234  112           129           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     5,6,                                                                          7-trinor-20-ethyl-8ξ-13-trans-prosteno                                     ate                                          235  112           132           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     5,6,                                                                          7,20-tetranor-16-methyl-8ξ-13-trans-pr                                     ost-                                                                          enoate                                       236  112           136           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     5,6,7-                                                                        trinor-19-isobutyl-8ξ-13-trans,18-pros                                     tadienoate                                   237  113           128           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     20-                                                                           methyl-8ξ-13-trans-prostenoate            238  113           134           ethyl 9-oxo-15-triphenylmethoxy-10a-homo-                                     19-                                                                           methyl-8ξ-13-trans,18-prostadienoate      239  114           125           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     s-                                                                            homo-20-nor-8ξ-13-trans-prostenoate       240  114           129           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     s-                                                                            homo-20-ethyl-8ξ-13-trans-prostenoate     241  114           132           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     s-                                                                            homo-16-methyl-20-nor-8ξ-13-trans-pros                                     tenoate                                      242  114           134           ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bi                                     s-                                                                            homo-19-methyl-8ξ-13-trans,18-prostadi                                     enoate                                       243  118           125           ethyl 9-oxo-15-triphenylmethoxy-3-thia-20                                     -nor-                                                                         8ξ-13-trans-prostenoate                   244  118           128           ethyl 9-oxo-15-triphenylmethoxy-3-thia-20                                     -methyl-                                                                      8ξ-13-trans-prostenoate                   245  118           130           ethyl 9-oxo-15-triphenylmethoxy-3-thia-16                                     -ethyl-                                                                       8ξ-13-trans-prostenoate                   246  118           133           ethyl 9-oxo-15-triphenylmethoxy-3-thia-16                                     -                                                                             methyl-18,19,20-trinor-8ξ-13-trans-pro                                     stenoate                                     247  118           134           ethyl 9-oxo-15-triphenylmethoxy-3-thia-19                                     -methyl-                                                                      8ξ-13-trans,18-prostadienoate             248  118           137           ethyl 9-oxo-15-triphenylmethoxy-3-thia-19                                     ,20-                                                                          dinor-8ξ-13-trans,17-prostadienoate       249  900           125           methyl 9-oxo-15-triphenylmethoxy-20-nor-8                                     ξ-5-                                                                       cis,13-trans-prostadienoate                  250  900           128           methyl 9-oxo-15-triphenylmethoxy-20-methy                                     l-8ξ  -5-                                                                  cis,13-trans-prostadienoate                  251  900           130           methyl 9-oxo-15-triphenylmethoxy-16-ethyl                                     -8ξ-5-                                                                     cis,13-trans-prostadienoate                  252  900           132           methyl 9-oxo-15-triphenylmethoxy-16-methy                                     l-20-                                                                         nor-8ξ-5-cis,13-trans-prostadienoate      253  900           134           methyl 9-oxo-15-triphenylmethoxy-19-methy                                     l-8ξ-5-                                                                    cis,13-trans,18-prostatrienoate              254  900           135           methyl 9-oxo-15-triphenylmethoxy-18,19-di                                     methyl-                                                                       8ξ-5-cis,13-trans,18-prostatrienoate      255  900           137           methyl 9-oxo-15-triphenylmethoxy-19,20-di                                     nor-8ξ-                                                                    5-cis,13-trans,17-prostatrienoate            256  900           139           methyl 9-oxo-15-triphenylmethoxy-8ξ-5-                                     cis,13-                                                                       trans,17-cis-prostatrienoate                 __________________________________________________________________________

EXAMPLE 257 Preparation of ethyl 9α/β,15-dihydroxy-13-trans-prostenoate

A solution containing 3 g. of ethyl 9-oxo-15-hydroxy-13-trans-prostenoate (Example 121) in 120 ml. of absolutealcohol containing 115 mg. of sodium borohydride is stirred at ambienttemperature for 18 hours. The solution is poured into 300 ml. ofsaturated sodium chloride solution and the oily precipitate is extractedwith ether. The ether is washed with saturated sodium chloride solution,dried with anhydrous magnesium sulfate and taken to dryness to givesubject product as an oil; λ max. 2195, 5178, 8.45 μ; the product is amixture of 9α- and 9β-hydroxy derivatives.

EXAMPLES 258- 374

Treatment of the designated 9-oxo-15-triphenylmethoxy derivatives listedin the table below, with glacial acetic acid-tetrahydropyran-water(4:2:1) in the manner described in Example 121 is productive of thecorresponding 15-hydroxy derivatives of the table. This acid treatmentalso ensures a trans-relationship between the two side-chains attachedto C₈ and C₁₂.

                  TABLE 4                                                         ______________________________________                                        Ex-   Starting 15-tri-                                                                            Product Alkyl 9-oxo-                                      ample phenylmethoxy 15-hydroxy-13-trans-                                            derivative of prostenoates                                                    Example                                                                 ______________________________________                                        258   140           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans-                                                        prostenoate                                               259   141           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans-prostenoate                                         260   142           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans-                                                             prostenoate                                               261   143           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans-                                                        prostenoate                                               262   144           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans-                                                               prostenoate                                               263   145           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans-                                                               prostenoate                                               264   146           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans-                                                            prostenoate                                               265   147           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans-                                                             prostenoate                                               266   148           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans-                                                            prostenoate                                               267   149           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans-                                                            prostenoate                                               268   150           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-13-trans-                                                            prostenoate                                               269   151           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans-prostenoate                                      270   152           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans-prostenoate                                         271   153           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans-prostenoate                                         272   154           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans                                                               prostenoate                                               273   155           Butyl 9-oxo-15-hydroxy-                                                       13-trans-prostenoate                                      274   156           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans-                                                             prostenoate                                               275   157           Methyl 9-oxo-15-hydroxy-                                                      13-trans-prostenoate                                      276   158           n-decyl 9-oxo-15-                                                             hydroxy-13-trans-                                                             prostenoate                                               277   159           Methyl 9-oxo-15-                                                              hydroxy-5-cis,-13-                                                            trans-prostadienoate                                      278   160           Ethyl 9-oxo-15-hydroxy-                                                       20-nor-13-trans-                                                              prostenoate                                               279   161           Ethyl 9-oxo-15-hydroxy-                                                       20-methyl-13-trans-                                                           prostenoate                                               280   162           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-13-trans-                                                            prostenoate                                               281   163           Ethyl 9-oxo-15-hydroxy-                                                       16-methyl-20-nor-13-                                                          trans-prostenoate                                         282   164           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-13-trans,18-                                                        prostadienoate                                            283   165           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-13-                                                            trans,18-prostadienoate                                   284   166           Ethyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                            285   167           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans,                                                        17-cis-prostadienoate                                     286   168           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-13-trans-                                                           17-cis-prostadienoate                                     287   169           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans,17-cis-prosta-                                                          dienoate                                                  288   170           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans,17-                                                          cis-prostadienoate                                        289   171           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans,                                                        17-cis-prostadienoate                                     290   172           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans,17-cis                                                         prostadienoate                                            291   173           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans,17-cis-                                                        prostadienoate                                            292   174           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans,17-                                                         cis-prostadienoate                                        293   175           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans,17-                                                          cis-prostadienoate                                        294   176           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans,17-                                                         cis-prostadienoate                                        295   177           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans,17-                                                         cis-prostadienoate                                        296   178           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-13-trans,17-                                                         cis-prostadienoate                                        297   179           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans,17-cis-prosta-                                                       dienoate                                                  298   180           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans,17-cis-prosta-                                                          dienoate                                                  299   181           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans,17-cis-prosta-                                                          dienoate                                                  300   182           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans,17-                                                           cis-prostadienoate                                        301   183           Butyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                            302   184           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans,17-                                                          cis-prostadienoate                                        303   185           Methyl 9-oxo-15-hydroxy-                                                      13-trans,17-cis                                                               prostadienoate                                            304   186           n-decyl 9-oxo-15-                                                             hydroxy-13-trans,17-                                                          cis-prostadienoate                                        305   187           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                            306   188           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7,19,20-pentanor-                                                         13-trans,17-prosta-                                                           dienoate                                                  307   189           Ethyl 9-oxo-15-hydroxy-                                                       19,20-dinor-13-trans,                                                         18-prostadienoate                                         308   190           Ethyl 9-oxo-15-hydroxy-                                                       17-methyl-20-isopro-                                                          penyl-13-trans-prosta-                                                        dienoate                                                  309   191           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-6,7,19,20-                                                           tetranor-13-trans-                                                            prostenoate                                               310   192           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-6,7-                                                           dinor-13-trans,18-                                                            prostadienoate                                            311   193           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-7a,7b-bishomo-                                                       13-trans-prostenoate                                      312   194           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-7a,7b-bis-                                                          homo-13-trans,18-                                                             prostadienoate                                            313   195           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          13-trans-prostenoate                                      314   196           Ethyl 9-oxo-15-hydroxy-                                                       2,20-diethyl-13-trans-                                                        prostenoate                                               315   197           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-methyl-20-                                                         nor-trans-prostenoate                                     316   198           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                                  317   199           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-18,19,20-                                                        trinor-13-trans-                                                              prostenoate                                               318   200           Ethyl 9-oxo-15-hydroxy-                                                       3,3,20-trimethyl-13-                                                          trans-prostenoate                                         319   201           Ethyl 9-oxo-15-hydroxy-                                                       3,3,16-trimethyl-20-                                                          nor-13-trans-prosta-                                                          noate                                                     320   202           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                            321   203           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-13-trans,17-                                                            prostadienoate                                            322   204           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-nor-13-trans-                                                        prostenoate                                               323   205           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-methyl-13-                                                           trans-prostenoate                                         324   206           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-ethyl-13-                                                            trans-prostenoate                                         325   207           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-methyl-20-                                                           nor-13-trans-                                                                 prostenoate                                               326   208           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-13-                                                         trans,17-prostadienoate                                   327   209           Ethyl 9-oxo-15-hydroxy-                                                       7,19,20-trinor-13-                                                            trans,17-prostadienoate                                   328   210           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoate                                                  329   211           Ethyl 9-oxo-15-hydroxy-                                                       7,18,19,20-tetranor-                                                          16-methyl-13-trans-                                                           prostenoate                                               330   212           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-nor-13-                                                           trans-prostenoate                                         331   213           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-ethyl-13-                                                         trans-prostenoate                                         332   214           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                               333   215           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-methyl-20-                                                        nor-13-trans-prostenoate                                  prostenoate                                                                   334   216           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19-methyl-13-                                                        trans,18-prostadienoate                                   335   217           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                                  336   218           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-19,20-dinor-                                                          13-trans,17-prosta-                                                           dienoate                                                  337   219           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-20-nor-13-                                                           trans-prostenoate                                         338   220           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-20-ethyl-13-                                                         trans-prostenoate                                         339   221           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-ethyl-13-                                                         trans-prostenoate                                         340   222           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-methyl-18,                                                        19,20-trinor-13-trans-                                                        prostenoate                                               341   223           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-18,19-di-                                                            methyl-13-trans,18-pro-                                                       stadienoate                                               342   224           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-20-nor-13-                                                           trans-prostenoate                                         343   225           Ethyl 9-oxo-15-hydroxy-                                                       2,20-dimethyl-13-trans-                                                       prostenoate                                               344   226           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                               345   227           Ethyl 9-oxo-15-hydroxy-                                                       2,19-dimethyl-13-trans,-                                                      18-prostadienoate                                         346   228           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                                  347   229           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-nor-13-                                                           trans-prostenoate                                         348   230           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                         349   231           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-ethyl-13-                                                         trans-prostenoate                                         350   232           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-18,19-dimethyl-                                                      13-trans,18-prosta-                                                           dienoate                                                  351   233           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                                  352   234           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        20-ethyl-13-trans-                                                            prostenoate                                               353   235           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7,20-                                                            tetranor-16-methyl-13-                                                        trans-prostenoate                                         354   236           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        19-isobutyl-13-trans,                                                         18-prostadienoate                                         355   237           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                         356   238           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19-methyl-13-                                                        trans,18-prostadienoate                                   357   239           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-nor-                                                        13-trans-prostenoate                                      358   240           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-                                                            ethyl-13-trans-pro-                                                           stenoate                                                  359   241           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            methyl-20-nor-13-trans-                                                       prostenoate                                               360   242           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-19-                                                            methyl-13-trans,18-                                                           prostadienoate                                            361   243           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-nor-13-trans-                                                       prostenoate                                               362   244           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-methyl-13-                                                          trans-prostenoate                                         363   245           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-ethyl-13-                                                           trans-prostenoate                                         364   246           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-methyl-18,19,                                                       20-trinor-13-trans-                                                           prostenoate                                               365   247           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19-methyl-13-                                                          trans,18-prostadienoate                                   366   248           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-13-                                                        trans,17-prostadienoate                                   367   249           Methyl 9-oxo-15-hydroxy-                                                      20-nor-5-cis,13-trans-                                                        prostadienoate                                            368   250           Methyl 9-oxo-15-hydroxy-                                                      20-methyl-5-cis,13-                                                           trans-prostadienoate                                      369   251           Methyl 9-oxo-15-hydroxy-                                                      16-ethyl-5-cis,13-                                                            trans-prostadienoate                                      370   252           Methyl 9-oxo-15-hydroxy-                                                      16-methyl-20-nor-5-cis,                                                       13-trans-prostadienoate                                   371   253           Methyl 9-oxo-15-hydroxy-                                                      19-methyl-5-cis,13-                                                           trans,18-prosta-                                                              trienoate                                                 372   254           Methyl 9-oxo-15-hydroxy-                                                      18,19-dimethyl-5-cis,                                                         13-trans,18-prosta-                                                           trienoate                                                 373   255           Methyl 9-oxo-15-hydroxy-                                                      19,20-dinor-5-cis,13-                                                         trans,17-prosta-                                                              trienoate                                                 374   256           Methyl 9-oxo-15-hydroxy-                                                      5-cis,13-trans,17-cis-                                                        prostatrienoate                                           ______________________________________                                    

EXAMPLES 375-491

Saponification of the alkyl esters designated in the following table bythe method described in Example 122 is productive of the prostenoicacids of the table.

                  Table 5                                                         ______________________________________                                              Starting alkyl 9-                                                                            Product                                                  Ex-   oxo-prostenoate                                                                              9-Oxo-15-hydroxy-13-                                     ample of example     trans-prostenoic acid                                    ______________________________________                                        375   258            9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans-pros-                                                         tenoic acid                                              376   259            9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans-pros-                                                        tenoic acid                                              377   260            9-oxo-15-hydroxy-2-                                                           ethyl-13-trans-pros-                                                          tenoic acid                                              378   261            9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans-                                                            prostenoic acid                                          379   262            9-oxo-15-hydroxy-3-oxa-                                                       13-trans-prostenoic                                                           acid                                                     380   263            9-oxo-15-hydroxy-7-nor-                                                       13-trans-prostenoic                                                           acid                                                     381   264            9-oxo-15-hydroxy-2-                                                           fluoro-13-trans-pros-                                                         tenoic acid                                              382   265            9-oxo-15-hydroxy-7a-                                                          homo-13-trans-pros-                                                           tenoic acid                                              383   266            9-oxo-15-hydroxy-2-                                                           phenyl-13-trans-pros-                                                         tenoic acid                                              384   267            9-oxo-15-hydroxy-2-                                                           methyl-13-trans-pros-                                                         tenoic acid                                              385   268            9-oxo-15-hydroxy-10a-                                                         homo-13-trans-pros-                                                           tenoic acid                                              386   269            9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans-prostenoic acid                                    387   270            9-oxo-15-hydroxy-10a-                                                         homo-7-nor-13-trans-                                                          prostenoic acid                                          388   271            9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans-                                                         prostenoic acid                                          389   272            9-oxo-15-hydroxy-3-                                                           thia-13-trans-pros-                                                           tenoic acid                                              390   273            9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                    391   274            9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                    392   275            9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                    393   276            9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                    394   277            9-oxo-15-hydroxy-5-cis,                                                       13-trans-prostadienoic                                                        acid                                                     395   278            9-oxo-15-hydroxy-20-nor-                                                      13-trans-prostenoic                                                           acid                                                     396   279            9-oxo-15-hydroxy-20-                                                          methyl-13-trans-pros-                                                         tenoic acid                                              397   280            9-oxo-15-hydroxy-16-                                                          ethyl-13-trans-pros-                                                          tenoic acid                                              398   281            9-oxo-15-hydroxy-16-                                                          methyl-20-nor-13-trans-                                                       prostenoic acid                                          399   282            9-oxo-15-hydroxy-19-                                                          methyl-trans,18-                                                              prostadienoic acid                                       400   283            9-oxo-15-hydroxy-18,19-                                                       dimethyl-13-trans,18-                                                         prostadienoic acid                                       401   284            9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                             402   285            9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans,17-cis-                                                       prostadienoic acid                                       403   286            9-oxo-15-hydroxy-6,7-di-                                                      nor-13-trans,17-cis-                                                          prostadienoic acid                                       404   287            9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans,17-                                                          cis-prostadienoic acid                                   405   288            9-oxo-15-hydroxy-2-                                                           ethyl-13-trans,17-cis-                                                        prostadienoic acid                                       406   289            9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans,17-                                                         cis-prostadienoic acid                                   407   290            9-oxo-15-hydroxy-3-oxa-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                           408   291            9-oxo-15-hydroxy-7-nor-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                           409   292            9-oxo-15-hydroxy-2-                                                           fluoro-13-trans,17-cis-                                                       prostadienoic acid                                       410   293            9-oxo-15-hydroxy-7a-                                                          homo-13-trans,17-cis-                                                         prostadienoic acid                                       411   294            9-oxo-15-hydroxy-2-                                                           phenyl-13-trans,17-cis-                                                       prostadienoic acid                                       412   295            9-oxo-15-hydroxy-2-                                                           methyl-13-trans,17-                                                           cis-prostadienoic acid                                   413   296            9-oxo-15-hydroxy-10a-                                                         homo-13-trans,17-cis-                                                         prostadienoic acid                                       414   297            9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans,17-cis-prosta-                                                          dienoic acid                                             415   298            9-oxo-15-hydroxy-10a-                                                         homo-7-nor-13-trans,-                                                         17-cis-prostadienoic                                                          acid                                                     416   299            9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans,-                                                        17-cis-prostadienoic                                                          acid                                                     417   300            9-oxo-15-hydroxy-3-thia-                                                      13-trans,17-cis-prosta-                                                       dienoic acid                                             418   301            9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                             419   302            9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                             420   303            9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                             421   304            9-oxo-15-hydroxy-13                                                           trans,17-cis-prosta-                                                          dienoic acid                                             422   305            9-oxo-15-hydroxy-5,6,7-                                                       trinor-19-isobutyl-13-                                                        trans,18-prostadienoic                                                        acid                                                     423   306            9-oxo-15-hydroxy-5,6,7,-                                                      19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                    424   307            9-oxo-15-hydroxy-19,20-                                                       dinor-13-trans,18-                                                            prostadienoic acid                                       425   308            9-oxo-15-hydroxy-17,-                                                         methyl-20-isopropenyl-                                                        13-trans-prostenoic                                                           acid                                                     426   309            9-oxo-15-hydroxy-16-                                                          ethyl-6,7,19,20-tetra-                                                        nor-13-trans-prostenoic                                                       acid                                                     427   310            9-oxo-15-hydroxy-18,19-                                                       dimethyl-6,7-dinor-13-                                                        trans,18-prostadienoic                                                        acid                                                     428   311            9-oxo-15-hydroxy-16-                                                          ethyl-7a,7b-bishomo-                                                          13-trans-prostenoic                                                           acid                                                     429   312            9-oxo-15-hydroxy-19-                                                          methyl-7a,7b-bishomo-                                                         13-trans,18-prosta-                                                           dienoic acid                                             430   313            9-oxo-15-hydroxy-2-                                                           ethyl-19,20-dinor-13-                                                         trans-prostenoic acid                                    431   314            9-oxo-15-hydroxy-2,20-                                                        diethyl-13-trans-pros-                                                        enoic acid                                               432   315            9-oxo-15-hydroxy-2-                                                           ethyl-16-methyl-20-nor-                                                       13-trans-prostenoic                                                           acid                                                     433   316            9-oxo-15-hydroxy-2-                                                           ethyl-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                             434   317            9-oxo-15-hydroxy-3,3-                                                         dimethyl-18,19,20-tri-                                                        nor-13-trans-prostenoic                                                       acid                                                     435   318            9-oxo-15-hydroxy-3,3-                                                         20-trimethyl-13-trans-                                                        prostenoic acid                                          436   319            9-oxo-15-hydroxy-3,3,-                                                        16-trimethyl-20-nor-13-                                                       trans-prostenoic acid                                    437   320            9-oxo-15-hydroxy-3,3-                                                         dimethyl-19-isobutyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                             438   321            9-oxo-15-hydroxy-3,3-                                                         dimethyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoic acid                                             439   322            9-oxo-15-hydroxy-3-oxa-                                                       20-nor-13-trans-prost-                                                        enoic acid                                               440   323            9-oxo-15-hydroxy-3-oxa-                                                       20-methyl-13-trans-                                                           prostenoic acid                                          441   324            9-oxo-15-hydroxy-3-oxa-                                                       16-ethyl-13-trans-                                                            prostenoic acid                                          442   325            9-oxo-15-hydroxy-3-oxa-                                                       16-methyl-20-nor-13-                                                          trans-prostenoic acid                                    443   326            9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                    444   327            9-oxo-15-hydroxy-7,19,-                                                       20-trinor-13-trans,17-                                                        prostadienoic acid                                       445   328            9-oxo-15-hydroxy-7-nor-                                                       18,19-dimethyl-13-                                                            trans,18-prostadienoic                                                        acid                                                     446   329            9-oxo-15-hydroxy-7,18,-                                                       19,20-tetranor-16-meth-                                                       yl-13-trans-prostenoic                                                        acid                                                     447   330            9-oxo-15-hydroxy-2-                                                           fluoro-20-nor-13-trans-                                                       prostenoic acid                                          448   331            9-oxo-15-hydroxy-2-                                                           fluoro-20-ethyl-13-                                                           trans-prostenoic acid                                    449   332            9-oxo-15-hydroxy-2-                                                           fluoro-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                              450   333            9-oxo-15-hydroxy-2-                                                           fluoro-16-methyl-20-                                                          nor-13-trans-pros-                                                            tenoic acid                                              451   334            9-oxo-15-hydroxy-2-                                                           fluoro-19-methyl-13-                                                          trans,18-prostadienoic                                                        acid                                                     452   335            9-oxo-15-hydroxy-7a-                                                          homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                             453   336            9-oxo-15-hydroxy-7a-                                                          homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                     454   337            9-oxo-15-hydroxy-2-                                                           phenyl-20-nor-13-trans-                                                       prostenoic acid                                          455   338            9-oxo-15-hydroxy-2-                                                           phenyl-20-ethyl-13-                                                           trans-prostenoic acid                                    456   339            9-oxo-15-hydroxy-2-                                                           phenyl-16-ethyl-13-                                                           trans-prostenoic acid                                    457   340            9-oxo-15-hydroxy-2-phen-                                                      yl-16-methyl-18,19,20-                                                        trinor-13-trans-pros-                                                         tenoic acid                                              458   341            9-oxo-15-hydroxy-2-                                                           phenyl-18,19-dimethyl-                                                        13-trans,18-prosta-                                                           dienoic acid                                             459   342            9-oxo-15-hydroxy-2-                                                           methyl-20-nor-13-trans-                                                       prostenoic acid                                          460   343            9-oxo-15-hydroxy-2,20-                                                        dimethyl-13-trans-                                                            prostenoic acid                                          461   344            9-oxo-15-hydroxy-2-                                                           methyl-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                              462   345            9-oxo-15-hydroxy-2,19-                                                        dimethyl-13-trans,18-                                                         prostadienoic acid                                       463   346            9-oxo-15-hydroxy-2-                                                           methyl-19,20-dinor-                                                           13-trans,17-prosta-                                                           dienoic acid                                             464   347            9-oxo-15-hydroxy-10a-                                                         homo-20-nor-13-trans-                                                         prostenoic acid                                          465   348            9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                    466   349            9-oxo-15-hydroxy-10a-                                                         homo-16-ethyl-13-trans-                                                       prostenoic acid                                          467   350            9-oxo-15-hydroxy-10a-                                                         homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                             468   351            9-oxo-15-hydroxy-10a-                                                         homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                     469   352            9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-20-                                                         ethyl-13-trans-pros-                                                          tenoic acid                                              470   353            9-oxo-15-hydroxy-10a-                                                         homo-5,6,7,20-tetra-                                                          nor-16-methyl-13-trans-                                                       prostenoic acid                                          471   354            9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-19-                                                         isobutyl-13-trans,18-                                                         prostadienoic acid                                       472   355            9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                    473   356            9-oxo-15-hydroxy-10a-                                                         homo-19-methyl-13-                                                            trans,18-prostadienoic                                                        acid                                                     474   357            9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-nor-13-                                                            trans-prostenoic acid                                    475   358            9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-ethyl-13-                                                          trans-prostenoic acid                                    476   359            9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-methyl-20-                                                         nor-13-trans-prostenoic                                                       acid                                                     477   360            9-oxo-15-hydroxy-7a,10a-                                                      bishomo-19-methyl-13-                                                         trans,18-prostadienoic                                                        acid                                                     478   361            9-oxo-15-hydroxy-3-thia-                                                      20-nor-13-trans-pros-                                                         tenoic acid                                              479   362            9-oxo-15-hydroxy-3-thia-                                                      20-methyl-13-trans-                                                           prostenoic acid                                          480   363            9-oxo-15-hydroxy-3-thia-                                                      16-ethyl-13-trans-                                                            prostenoic acid                                          481   364            9-oxo-15-hydroxy-3-thia-                                                      16-methyl-18,19,20-                                                           trinor-13-trans-pros-                                                         tenoic acid                                              482   365            9-oxo-15-hydroxy-3-thia-                                                      19-methyl-13-trans,18-                                                        prostadienoic acid                                       483   366            9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                    484   367            9-oxo-15-hydroxy-20-nor-                                                      5-cis,13-trans-prosta-                                                        dienoic acid                                             485   368            9-oxo-15-hydroxy-20-                                                          methyl-5-cis,13-trans-                                                        prostadienoic acid                                       486   369            9-oxo-15-hydroxy-16-                                                          ethyl-5-cis,13-trans-                                                         prostadienoic acid                                       487   370            9-oxo-15-hydroxy-16-                                                          methyl-20-nor-5-cis,13-                                                       trans-prostadienoic                                                           acid                                                     488   371            9-oxo-15-hydroxy-19-                                                          methyl-5-cis,13-trans,-                                                       18-prostatrienoic acid                                   489   372            9-oxo-15-hydroxy-18,19-                                                       dimethyl-5-cis,13-                                                            trans-18-prostatrienoic                                                       acid                                                     490   373            9-oxo-15-hydroxy-19,20-                                                       dinor-5-cis,13-trans,-                                                        17-prostatrienoic acid                                   491   374            9-oxo-15-hydroxy-5-cis,-                                                      13-trans,17-cis-prosta-                                                       trienoic acid                                            ______________________________________                                    

EXAMPLE 492 Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org.Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbledisobutylene at a fast rate until the solution is saturated. The solutionis cooled and 2 ml. of concentrated sulfuric acid is added. The additionis stoppered and allowed to stand at room temperature for 3 days. Afterthe solution is poured into 300 ml. of 5% sodium carbonate, the organicphase is separated, washed with brine, dried with anhydrous magnesiumsulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) ofproduct, b.p. 59°C. (0.008 mm).

EXAMPLE 493 Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g.of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether undernitrogen atmosphere, is added 4.0 g. of copperiodide-tri-n-butylphosphine complex followed by dropwise addition of 49g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv.Chim. Acta 50, 2501(1967)] and the resulting mixture is stirred for 18hours. Saturated ammonium chloride (110 ml.) is added followed by 100ml. of water and 100 ml. of diethyl ether. Unreacted magnesium isremoved by filtration. The ethereal layer is washed successively withaqueous sodium thiosulfate solution, ammonium chloride solution, andwater, dried over magnesium sulfate and taken to dryness to give an oil.Distillation at 0.05 mm. (bath 100°-185°C. ) gives 45.4 g. of materialcontaining unreacted starting material and 30 g. (85% yield based onnon-recovered starting material; see below) of residue which containsthe desired product. This material is chromatographed on silica gel. Theproduct is eluted with diethyl ether to give 25.2 g. (71% based onrecovered starting material) of a syrup; this material has nosignificant ultraviolet absorption; λ_(max) ^(KBr) 5.74, 7.20, 7,35,8.35 μ; nrm 2H quartet δ 4.09 (OCH₂ of ester), 1H broad singlet 3.57(carbinolic proton), 5H overlapping multiplets 2.0- 2.4 (protons next toC=O). 3H triplet 1.22 (CH₃ of ethyl), 9H singlet 1.17 (CH₃ 's tot-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

EXAMPLE 494 Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1hour and is then poured into 500 ml. of ice water and extracted severaltimes with chloroform. The combined chloroform extracts are washed withsaturated sodium bicarbonate solution, saturated sodium chloridesolution, dried with anhydrous magnesium sulfate, and taken to dryness.The resulting oil is dissolved in 200 ml. of 1N ammonium hydroxide inethanol, kept at ambient temperature for 15 minutes, then taken todryness. The residual oil is dissolved in chloroform and washed with 1Nhydrochloric acid, saturated sodium chloride solution, dried and takento dryness to give 21.7 g. (100%) of product as a yellow syrup. There isessentially no uv absorption; λ_(max) ^(KBr) 2.90, 5.75, 8.45 μ; nmr 2Hquartet δ 4.13 (OCH₂ of ester), 1H broad singlet 3.63 (carbinolicproton), 3H triplet (CH₃ of ester), and 3H distorted triplet 0.92(terminal methyl); mass spectrum: m/e 3.68.

EXAMPLE 495 Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester in230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassiumhydroxide is stirred at 50°C. for 1 hour and then at room temperaturefor 18 hours. The resulting solution is acidified with 1N hydrochloricacid, saturated with sodium chloride, and extracted several times withdiethyl ether. The combined ether extracts are washed twice withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate, and taken to dryness to give 13.1 g. (94%) of product as anoil. There is essentially no uv absorption; [α]_(D) ²⁵ O° (1.0% inCHCl₃); λ_(max) ^(KBr) 2.80-3.70 (broad), 5.75, 5.87 μ; nrm 2H singlet δ6.65 (hydroxyl and carboxyl protons), 1H broad singlet 3.63 (carbinolicproton), and 3H distorted triplet 0.93 (terminal methyl); mass spectrum:m/e 340.

EXAMPLE 496 Preparation of 1-chloro-3-hydroxy-4-octyne

To 68 ml. of 1.6M butyllithium in hexane at -50°C. is added dropwise,with stirring, 7.4 g. of 1-pentyne. The resulting white sludge isdiluted with 20 ml. of hexane, brought to 10°C. and treated with 11 g.of freshly prepared β -chloropropionaldehyde (Org. Syn., Coll. Vol. I,p. 166) at such a rate that the temperature is maintained at 10°-15°C.The solution is allowed to stir at ambient temperature for 18 hours thentreated with saturated ammonium chloride solution. The organic phase isseparated, washed with dilute hydrochloric solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives 5.1g. of product b.p. 65°-66°C. at 0.3 nm.; λ max. 2.95 (--OH) and 4.55 μ(-C.tbd.C-); vapor phase chromatography shows one peak.

EXAMPLE 497 Preparation of 1-chloro-3-hydroxy-4-cis-octene

A solution of 2 g. of 1-chloro-3-hydroxy-4-octyne (Example 496) ishydrogenated in 50 ml. absolute alcohol using 200 mg. of Lindlarcatalyst (5% Pd on CaCo₃). The catalyst is removed by filtration and themother liquor is taken to dryness to give 2 g. of an oil; λ max. 2.95(--OH) and 7.25 μ (cis ##EQU20##

EXAMPLE 498 Preparation of 3-hydroxy-1-iodo-4-octyne

A mixture of 15 g. of sodium iodide in 100 ml. of 2-butanone is stirredat the reflux temperature for 30 minutes. To the cooled mixture is added12 g. of 1-chloro-3-hydroxy-4-octyne in 150 ml. of 2-butanone. Theresulting mixture is stirred at the reflux temperature for 18 hours thencooled and filtered. The mother liquor is taken to dryness and theresidue is triturated with benzene and filtered. The benzene is taken todryness to give the subject product as an oil. The material is shown tobe homogeneous by vapor phase chromatography and thin layerchromatography.

EXAMPLE 499 Preparation of 3-hydroxy-1-iodo-4-cis-octen

The subject compound is prepared from 3-hydroxy-1-chloro-4-cis-octeneand sodium iodide by the method of Example 498.

EXAMPLE 500 Preparation of 3-t-butoxy-1-iodo-4-octyne

The subject compound is prepared from 3-hydroxy-1-iodo-4-octyne (Example498) and isobutylene by the method of Example 492.

EXAMPLE 501 Preparation of 3-t-butoxy-1-iodo-4-cis-octene

The subject compound is prepared from 3-hydroxy-1-iodo-4-cis-octene(Example 499) and isobutylene by the method of Example 492.

EXAMPLE 502 Preparation of 3-(tert-butoxy)-1-iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et. al., Bull.Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing30 g. of sodium iodide is stirred at the reflux temperature for 18hours. The cooled solution is filtered and the mother liquor is taken todryness. Distillation of the residue affords 32.9 g. (84%) of1-iodo-3-hexanol, b.p. 105°C (10 mm). Treatment of this material in 500ml. of methylene chloride, containing 4 ml. of concentrated sulfuricacid, with isobutylene according to the procedure described in Example492 gives 27 g. of crude material. Chromatography on florisil affords 16g. of product; λmax. 7.22 and 7.37 μ (tert-butyl group).

EXAMPLES 503-558

Treatment of the cyclopentenones designated in the table below with thedesignated Grignard reagents by the procedure of Example 493 isproductive of the alkyl 9-oxo-15-t-butoxy-8ξ -prostanoates andprostenoates of the table. 3-t-Butoxyoctylmagnesium iodide was preparedfrom 3-t-butoxy-1-iodooctane (Example 492); 3-t-butoxyhexyl magnesiumiodide was prepared from 3-t-butoxy-1-iodohexane (Example 502),3-t-butoxy-4-octynyl magnesium iodide was prepared from3-butoxy-1-iodo-4-octyne (Example 500); and 3-t-butoxy-4-cis-octenylmagnesium iodide was prepared from 3-t-butoxy-1-iodo-4-cis-octene(Example 501).

                                      Table 8                                     __________________________________________________________________________         Starting cyclopentenone Product Alkyl 9-Oxo-15-t-butoxy-8ξ-prostan                                 oates,                                           Example                                                                            of Example   Grignard Reagent                                                                         prostynoates and prostenoates                    __________________________________________________________________________    503  31           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-prostan                                 oate                                                               magnesium iodide                                            504  41           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ                         magnesium iodide                                                                         prostanoate                                      505  46           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-prostanoa                                 te                                                                 magnesium iodide                                            506  70           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-prosta                                 noate                                                              magnesium iodide                                            507  79           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-prosta                                 noate                                                              magnesium iodide                                            508  99           3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-prosta                                 noate                                                              magnesium iodide                                            509  118          3-t-butoxyoctyl                                                                          ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-prostano                                 ate                                                                magnesium iodide                                            510  900          3-t-butoxyoctyl                                                                          methyl 9-oxo-15-t-butoxy-8ξ-5-cis-prosteno                                 ate                                                                magnesium iodide                                            511  31           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-2-ethyl-19,20-dinor-8                                 ξ-                                                              magnesium iodide                                                                         prostanoate                                      512  41           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-19,20-                        magnesium iodide                                                                         dinor-8ξ-prostanoate                          513  46           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-3-oxa-19,20-dinor-8.x                                 i.-                                                                magnesium iodide                                                                         prostanoate                                      514  70           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-2-fluoro-19,20-dinor-                                 8ξ-                                                             magnesium iodide                                                                         prostanoate                                      515  79           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-2-phenyl-19,20-dinor-                                 8ξ-                                                             magnesium iodide                                                                         prostanoate                                      516  99           3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-2-methyl-19,20-dinor-                                 8ξ-                                                             magnesium iodide                                                                         prostanoate                                      517  118          3-t-butoxyhexyl                                                                          ethyl 9-oxo-15-t-butoxy-3-thia-19,20-dinor-8.                                 xi.-                                                               magnesium iodide                                                                         prostanoate                                      518  900          3-t-butoxyhexyl                                                                          methyl 9-oxo-15-t-butoxy-19,20-dinor-8ξ-5-                                 cis-                                                               magnesium iodide                                                                         prostenoate                                      519  13           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                       ynyl magnesium                                                                iodide                                                      520  15           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-                        ynyl magnesium                                                                           prostynoate                                                        iodide                                                      521  23           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-1                                 6-                                                                 ynyl magnesium                                                                           prostynoate                                                        iodide                                                      522  31           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-pros                                 tynoate                                                            ynyl magnesium                                                                iodide                                                      523  41           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16                                 -                                                                  ynyl magnesium                                              prostynoate                                                                                     iodide                                                      524  46           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-prosty                                 noate                                                              ynyl magnesium                                                                iodide                                                      525  53           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-prosty                                 noate                                                              ynyl magnesium                                                                iodide                                                      526  70           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-pro                                 stynoate                                                           ynyl magnesium                                                                iodide                                                      527  74           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-pros                                 tynoate                                                            ynyl magnesium                                                                iodide                                                      528  79           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-pro                                 stynoate                                                           ynyl magnesiium                                                               iodide                                                      529  81           3-t-butoxy-4-oct-                                                                        butyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                                  O                                                                  ynyl magnesium                                                                iodide                                                      530  82           3-t-butoxy-4-oct-                                                                        isopropyl 9-oxo-15-t-butoxy-8ξ-16-prostyno                                 ate                                                                ynyl magnesium                                                                iodide                                                      531  83           3-t-butoxy-4-oct-                                                                        methyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                      ynyl magnesium                                                                iodide                                                      532  84           3-t-butoxy-4-oct-                                                                        decyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                       ynyl magnesium                                                                iodide                                                      533  99           3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-pro                                 stynoate                                                           ynyl magnesium                                                                iodide                                                      534  118          3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-prost                                 ynoate                                                             ynyl magnesium                                                                iodide                                                      535  111          3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-pro                                 stynoate                                                           ynyl magnesium                                                                iodide                                                      536  113          3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-                                 16-                                                                ynyl magnesium                                                                           prostynoate                                                        iodide                                                      537  114          3-t-butoxy-4-oct-                                                                        ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-                                 16-                                                                ynyl magnesium                                                                           prostynoate                                                        iodide                                                      538  900          3-t-butoxy-4-oct-                                                                        methyl 9-oxo-15-t-butoxy-8ξ-16-yne-5-cis-                                  F                                                                  ynyl magnesium                                                                           prostenoate                                                        iodide                                                      539  13           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosteno                                 ate                                                                octenyl magnesium                                                             iodide                                                      540  15           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-ci                                 s-                                                                 octenyl magnesium                                                                        prostenoate                                                        iodide                                                      541  23           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-1                                 6-                                                                 octenyl magnesium                                                                        cis-prostenoate                                                    iodide                                                      542  31           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-cis-                                 2                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      543  41           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16                                 -cis-                                                              octenyl magnesium                                                                        prostenoate                                                        iodide                                                      544  46           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-cis-                        octenyl magnesium                                                                        prostenoate                                                        iodide                                                      545  53           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-cis-                        octenyl magnesium                                                                        prostenoate                                                        iodide                                                      546  70           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-cis                                 -                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      547  74           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-cis-                                 r                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      548  79           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-cis                                 -                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      549  81           3-t-butoxy-4-cis-                                                                        butyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosteno                                 ate                                                                octenyl magnesium                                                             iodide                                                      550  82           3-t-butoxy-4-cis-                                                                        isopropyl 9-oxo-15-t-butoxy-8ξ-16-cis-                          octenyl magnesium                                                                        prostenoate                                                        iodide                                                      551  83           3-t-butoxy-4-cis-                                                                        methyl 9-oxo-15-t-butoxy-8ξ-16-cis-                             octenyl magnesium                                                                        prostenoate                                                        iodide                                                      552  84           3-t-butoxy-4-cis-                                                                        decyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosteno                                 ate                                                                ocentyl magnesium                                                             iodide                                                      553  99           3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-cis                                 -                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      554  118          3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-cis-                                  r                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      555  111          3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-cis                                 -                                                                  octenyl magnesium                                                                        prostenoate                                                        iodide                                                      556  113          3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-                                 16-                                                                octenyl magnesium                                                                        cis-prostenoate                                                    iodide                                                      557  114          3-t-butoxy-4-cis-                                                                        ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-                                 16-                                                                octenyl magnesium                                                                        cis-prostenoate                                                    iodide                                                      558  900          3-t-butoxy-4-cis-                                                                        methyl 9-oxo-15-t-butoxy-8ξ-5-cis-16-cis-                                  a                                                                  octenyl magnesium                                                                        prostadienoate                                                     iodide                                                      __________________________________________________________________________

EXAMPLES 559-614

Treatment of the 9-oxo-15-t-butoxy derivatives designated in the tablebelow with trifluoroacetic acid and then with aqueous ammonia by themethod described in Example 494 is productive of the 9-oxo-15-hydroxyesters of the table.

                  TABLE 7                                                         ______________________________________                                              Starting 15-t-                                                          Ex-   butoxy derivative                                                                            Product Alkyl 9-oxo-15-                                  ample of Example     hydroxy derivative                                       ______________________________________                                        559   503            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-prostanoate                                      560   504            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-prostano-                                                        ate                                                      561   505            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-prostanoate                                        562   506            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-prostanoate                                     563   507            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-prostanoate                                     564   508            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-prostanoate                                     565   509            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-prostanoate                                       566   510            Methyl 9-oxo-15-hydroxy-                                                      5-cis-prostenoate                                        567   511            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          prostanoate                                              568   512            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-prostanoate                                        569   513            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-                                                            prostanoate                                              570   514            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19,20-dinor-                                                         prostanoate                                              571   515            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-19,20-dinor-                                                         prostanoate                                              572   516            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         prostanoate                                              573   517            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-                                                           prostanoate                                              574   518            Methyl 9-oxo-15-hydroxy-                                                      19,20-dinor-5-cis-                                                            prostenoate                                              575   519            Ethyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                           576   520            Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-prostyno-                                                        ate                                                      577   521            Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-prost-                                                       ynoate                                                   578   522            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-prostynoate                                   579   523            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-prost-                                                        ynoate                                                   580   524            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-prostynoate                                     581   525            Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-prostynoate                                     582   526            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-prostynoate                                  583   527            Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-prostynoate                                   584   528            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-prostynoate                                  585   529            Butyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                           586   530            Isopropyl 9-oxo-15-hy-                                                        droxy-16-prostynoate                                     587   531            Methyl 9-oxo-15-hydroxy-                                                      16-prostynoate                                           588   532            Decyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                           589   533            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-prostynoate                                  590   534            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-prostynoate                                    591   535            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-prostynoate                                  592   536            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-                                                            prostynoate                                              593   537            Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            prostynoate                                              594   538            Methyl 9-oxo-15-hydroxy-                                                      16-yne-5-cis-prostenoate                                 595   539            Ethyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                       596   540            Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-cis-pros-                                                        tenoate                                                  597   541            Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-cis-                                                         prostenoate                                              598   542            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-cis-prosteno-                                                      ate                                                      599   543            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-cis-                                                          prostenoate                                              600   544            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-cis-prostenoate                                 601   545            Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-cis-prostenoate                                 602   546            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-cis-prosten-                                                      oate                                                     603   547            Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-cis-prosten-                                                       oate                                                     604   548            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-cis-prosten-                                                      oate                                                     605   549            Butyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                       606   550            Isopropyl 9-oxo-15-hy-                                                        droxy-16-cis-prostenoate                                 607   551            Methyl 9-oxo-15-hydroxy-                                                      16-cis-prostenoate                                       608   552            Decyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                       609   553            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-cis-pros-                                                         tenoate                                                  610   554            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-cis-prosteno-                                                       ate                                                      611   555            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-cis-pros-                                                         tenoate                                                  612   556            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-cis-                                                        prostenoate                                              613   557            Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-cis-                                                        prostenoate                                              614   558            Methyl 9-oxo-15-hydroxy-                                                      5-cis-16-cis-prostadi-                                                        enoate                                                   ______________________________________                                    

EXAMPLES 615-662

Saponification of the 9-oxo-15-hydroxy alkyl esters designated in thetable below by the procedure described in Example 495 is productive ofthe carboxylic acids of the table.

                  TABLE 8                                                         ______________________________________                                              Starting alkyl                                                          Ex-   ester of     Product 9-oxo-15-hydroxy-                                  ample Example      prostanoic acid                                            ______________________________________                                        615   559          9-oxo-15-hydroxy-2-ethyl-                                                     prostanoic acid                                            616   560          9-oxo-15-hydroxy-3,3-di-                                                      methyl-prostanoic acid                                     617   561          9-oxo-15-hydroxy-3-oxa-                                                       prostanoic acid                                            618   562          9-oxo-15-hydroxy-2-fluoro-                                                    prostanoic acid                                            619   563          9-oxo-15-hydroxy-2-phenyl-                                                    prostanoic acid                                            620   564          9-oxo-15-hydroxy-2-methyl-                                                    prostanoic acid                                            621   565          9-oxo-15-hydroxy-3-thia-                                                      prostanoic acid                                            622   566          9-oxo-15-hydroxy-5-cis-                                                       prostenoic acid                                            623   567          9-oxo-15-hydroxy-2-ethyl-                                                     19,20-dinor-prostanoic                                                        acid                                                       624   568          9-oxo-15-3,3-dimethyl-19,                                                     20-dinor-prostanoic acid                                   625   569          9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-prostanoic                                                        acid                                                       626   570          9-oxo-15-hydroxy-2-fluoro-                                                    19,20-dinor-prostanoic                                                        acid                                                       627   571          9-oxo-15-hydroxy-2-phenyl-                                                    19,20-dinor-prostanoic                                                        acid                                                       628   572          9-oxo-15-hydroxy-2-methyl-                                                    19,20-dinor-prostanoic                                                        acid                                                       629   573          9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-prostanoic                                                        acid                                                       630   574          9-oxo-15-hydroxy-19,20-                                                       dinor-5-cis-prostenoic acid                                631   575          9-oxo-15-hydroxy-16-pros-                                                     tynoic acid                                                632   576          9-oxo-15-hydroxy-6,7-dinor-                                                   16-prostynoic acid                                         633   577          9-oxo-15-hydoxy-7a,7b-bis-                                                    homo-16-prostynoic acid                                    634   578          9-oxo-15-hydroxy-2-ethyl-                                                     16-prostynoic acid                                         635   579          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-prostynoic acid                                  636   580          9-oxo-15-hydroxy-3-oxa-16-                                                    prostynoic acid                                            637   581          9-oxo-15-hydroxy-7-nor-16-                                                    prostynoic acid                                            638   582          9-oxo-15-hydroxy-2-fluoro-                                                    16-prostynoic acid                                         639   583          9-oxo-15-hydroxy-7a-homo-                                                     16-prostynoic acid                                         640   584          9-oxo-15-hydroxy-2-phenyl-                                                    16-prostynoic acid                                         641   589          9-oxo-15-hydroxy-2-methyl-                                                    16-prostynoic acid                                         642   590          9-oxo-15-hydroxy-3-thia-                                                      16-prostynoic acid                                         643   591          9-oxo-15-hydroxy-10a-homo-                                                    16-prostynoic acid                                         644   592          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-prostynoic acid                                   645   593          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-prostynoic acid                                 646   594          9-oxo-15-hydroxy-16-yne-5-                                                    cis-prostenoic acid                                        647   595          9-oxo-15-hydroxy-16-cis-                                                      prostenoic acid                                            648   596          9-oxo-15-hydroxy-6,7-dinor-                                                   16-cis-prostenoic acid                                     649   597          9-oxo-15-hydroxy-7a,7b-bis-                                                   homo-16-cis-prostenoic acid                                650   598          9-oxo-15-hydroxy-2-ethyl-                                                     16-cis-prostenoic acid                                     651   599          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-cis-prostenoic                                                      acid                                                       652   600          9-oxo-15-hydroxy-3-oxa-16-                                                    cis-prostenoic acid                                        653   601          9-oxo-15-hydroxy-7-nor-16-                                                    cis-prostenoic acid                                        654   602          9-oxo-15-hydroxy-2-fluoro-                                                    16-cis-prostenoic acid                                     655   603          9-oxo-15-hydroxy-7a-homo-                                                     16-cis-prostenoic acid                                     656   604          9-oxo-15-hydroxy-2-phenyl-                                                    16-cis-prostenoic acid                                     657   609          9-oxo-15-hydroxy-2-methyl-                                                    16-cis-prostenoic acid                                     658   610          9-oxo-15-hydroxy-3-thia-                                                      16-cis-prostenoic acid                                     659   611          9-oxo-15-hydroxy-10a-homo-                                                    16-cis-prostenoic acid                                     660   612          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-cis-prostenoic                                                       acid                                                       661   613          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-cis-prosten-                                                       oic acid                                                   662   614          9-oxo-15-hydroxy-5-cis-                                                       16-cis-prostadienoic                                                          acid                                                       ______________________________________                                    

EXAMPLE 663 Ethyl 9-oxo-15-hydroxy-16-trans-prostenoate

To a mixture of 1 g. of ethyl 9-oxo-15-hydroxy-16-prostynoate (Example575), 11 ml. of water and 27 ml. of dimethylformamide is added 27 ml. of0.45 N chromous sulfate solution. The mixture is stirred for 48 hoursunder nitrogen atmosphere. The mixture then is extracted with etherseveral times and the combined extracts are taken to dryness. Silica gelchromatography gives the subject product as an oil.

EXAMPLES 664- 682

Treatment of the 9-oxo-15-hydroxy-16-prostynoates listed in Table 8Abelow with chromous sulfate in the manner of Example 663 is productiveof the product 9-oxo-15-hydroxy-16-trans-prostenoates of the table.

                  TABLE 8A                                                        ______________________________________                                              Starting       Product                                                  Ex-   16-prostenoate 9-oxo-15-hydroxy-16-                                     ample of Example     trans-prostenoate                                        ______________________________________                                        664   576            Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-trans-                                                           prostenoate                                              665   577            Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-trans-                                                       prostenoate                                              666   578            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-trans-pros-                                                        tenoate                                                  667   579            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-trans-                                                        prostenoate                                              668   580            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-trans-prosten-                                                       oate                                                     669   581            Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-trans-pros-                                                          tenoate                                                  670   582            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-trans-pros-                                                       tenoate                                                  671   583            Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-trans-pros-                                                        tenoate                                                  672   584            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-trans-pros-                                                       tenoate                                                  673   585            Butyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                     674   586            Isopropyl 9-oxo-15-                                                           hydroxy-16-trans-pros-                                                        tenoate                                                  675   587            Methyl 9-oxo-15-hydroxy-                                                      16-trans-prostenoate                                     676   588            Decyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                     677   589            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-trans-pros-                                                       tenoate                                                  678   590            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-trans-pros-                                                         tenoate                                                  679   591            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-trans-pros-                                                       tenoate                                                  680   592            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-trans-                                                      prostenoate                                              681   593            Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-trans-                                                      prostenoate                                              682   594            Methyl 9-oxo-15-hydroxy-                                                      5-cis,16-trans-prosta-                                                        dienoate                                                 ______________________________________                                    

EXAMPLES 683-698

Saponification of the alkyl 9-oxo-15-hydroxy-16-trans-prostenoateslisted in Table 8b below by the procedure described in Example 495 isproductive of the corresponding prostenoic acids of the table.

                  TABLE 8B                                                        ______________________________________                                              Starting     Product 9-oxo-15-                                          Ex-   alkyl ester  hydroxy-16-trans                                           ample of Example   prostenoic acids                                           ______________________________________                                        683   663          9-oxo-15-hydroxy-16-                                                          trans-prostenoic acid                                      684   664          9-oxo-15-hydroxy-6,7-                                                         dinor-16-trans-prosten-                                                       oic acid                                                   685   665          9-oxo-15-hydroxy-7a,7b-                                                       bishomo-16-trans-pros-                                                        tenoic acid                                                686   666          9-oxo-15-hydroxy-2-                                                           ethyl-16-trans-prosten-                                                       oic acid                                                   687   667          9-oxo-15-hydroxy-3,3-                                                         dimethyl-16-trans-pros-                                                       tenoic acid                                                688   668          9-oxo-15-hydroxy-3-oxa-                                                       16-trans-prostenoic acid                                   689   669          9-oxo-15-hydroxy-7-nor-                                                       16-trans-prostenoic acid                                   690   670          9-oxo-15-hydroxy-2-                                                           fluoro-16-trans-pros-                                                         tenoic acid                                                691   671          9-oxo-15-hydroxy-7a-                                                          homo-16-trans-prostenoic                                                      acid                                                       692   672          9-oxo-15-hydroxy-2-                                                           phenyl-16-trans-pros-                                                         tenoic acid                                                693   677          9-oxo-15-hydroxy-2-meth-                                                      yl-16-prostenoic                                                              acid                                                       694   678          9-oxo-15-hydroxy-3-thia-                                                      16-trans-prostenoic acid                                   695   679          9-oxo-15-hydroxy-10a-                                                         homo-16-trans-prostenoic                                                      acid                                                       696   680          9-oxo-15-hydroxy-10a-                                                         homo-7-nor-16-trans-                                                          prostenoic acid                                            697   681          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-trans-pro-                                                         stenoic acid                                               698   682          9-oxo-15-hydroxy-5-cis,                                                       16-trans-prostadienoic                                                        acid                                                       ______________________________________                                    

EXAMPLE 699 Preparation of 9-oxo-15-hydroxy-3,3-dimethylprostanoic acid

A 2 g. sample of 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acidis hydrogenated using 700 mg. of 10% palladium on carbon in 50 ml. ofabsolute alcohol. The catalyst is removed by filtration and the motherliquor is taken to dryness to give 2 g. of subject compound as an oil.

EXAMPLE 723 Preparation of 1-chloro-trans-1-octen-3-one

To a slurry of 233.5 g. (1.75 moles) of aluminum chloride in 390 ml. ofcarbon tetrachloride, saturated with acetylene and cooled in an icebath, is added over 20 minutes 201.9 g. (1.50 moles) of hexanoylchloride. After the addition is complete, acetylene is bubbled into themixture as rapidly as it is absorbed and for 1 hour after absorptionbecomes slow. The mixture is poured onto 1700 g. of ice and 720 ml. ofsaturated brine. The organic phase is separated and the aqueous phase iswashed with ether. The combined organic phase and washings as washedwith saturated brine, dried (Na₂ SO₄) and evaporated. The residual oilis combined with 10 g. of hydroquinone and distilled to yield acolorless oil, b.p. 51°-52°C. (0.10 torr).

EXAMPLE 724 Preparation of 1-iodo-trans-1-octen-3-one

A mixture of 54.5 g. (0.364 mole) of sodium iodide and 40 g. (0.249mole) of 1-chloro-trans-1-octen 3-one (Example 723) in 360 ml. ofacetone is stirred and refluxed for 24 hours. The reaction mixture iscooled, filtered and concentrated. The residue is partitioned betweenwater and ether. The organic phase is washed with dilute sodiumbicarbonate solution, brine, dried (MgSO₄) and evaporated to an oil.This material is used directly without purification.

EXAMPLE 725 Preparation of 1-bromo-trans-1-octen-3 one

A mixture of 68.0 g. (0.424 mole) of 1-chloro-trans-1-octen-3 one(Example 723) and 444 g. (4.24 moles) of anhydrous lithium bromide in900 ml. of 2-pentanone is refluxed for 30 minutes, cooled, andpartitioned between ice water and ether. The organic phase is washedwith water and saturated brine, dried (NaSO₄), and evaporated to an oil.This material is used directly without purification.

EXAMPLE 726 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 14.29 g. (0.378 mole) of sodium borohydridein 400 ml. of anhydrous ethanol is added the crude1-bromo-trans-1-octen-3-one (Example 725), from 0.424 mole of1-chloro-trans-1-octen-3-one) over 30 minutes. The mixture is stirredfor 2 hours with ice cooling and is then partitioned between ice waterand benzene. The organic phase is washed with water and saturated brine,dried (Na₂ SO₄), and evaporated to an oil. Fractional distillationyields the title compound as a colorless oil, b.p. 66°-68°C. (0.025torr).

EXAMPLE 727 Preparation of 1-chloro-trans-1-octen-3-ol

Treatment of 1-chloro-trans-1-octen-3-one (Example 723) with sodiumborohydride in the manner of Example 726 is productive of the subjectcompound.

EXAMPLE 728 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-octene

A mixture of 6.212 g. (0.030 mole) of 1-bromo-trans-1-octen-3-ol(Example 726) and 10.67 g. (0.033 mole) of triphenylmethyl bromide in 40ml. of pyridine is heated to 100°C. for 1.5 hours under an inertatmosphere. The mixture is cooled and filtered. The filtrate ispartitioned between ice water and ether. The organic phase is washedwith cold dilute hydrochloric acid, saturated sodium bicarbonatesolution, and saturated brine, dried (NaSO₄), and evaporated to an oil.The latter is dissolved in hexane and passed through 250 g. of Florisilto yield after evaporation a colorless oil. Found for C₂₇ H₂₉ OBr : C,72.13; H, 6.61; Br. 17.57.

EXAMPLE 729 Preparation of 1-iodo-trans-1-octen-3-ol

Treatment of 63 g. (0.25 mole) of 1-iodo-trans-1-octen-3-one (Example724) with sodium borohydride in the manner described in Example 726 gave58 g. of yellow oil. The oil is purified by adsorption chromatography ona magnesia silica gel column using benzene as eluent to give a lightyellow oil.

EXAMPLE 730 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 7.62 g. (0.03 mole) of 1 -iodo-trans-1-octen-3-ol with10.67 g. (0.033 mole) of triphenylmethyl bromide in pyridine in themanner described in Example 728 gave 13.448 g. (90%) of a colorless oil.

EXAMPLE 731 Preparation of 1-chloro-3-triphenylmethoxy-trans-1-octene

Treatment of 1-chloro-trans-1-octen-3-ol (Example 727) withtriphenylmethyl chloride by the method described in Example 728 exceptthat the heating period is extended to six hours provides the subjectcompound.

EXAMPLE 732 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.535 g. (0.022 g. atom) of magnesium in 6 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 6.548 g. (0.01455 mole) of 1-bromo-3-trityloxy-trans-1-octene(Example 728) in 8 ml. of tetrahydrofuran. Reaction is initiated bywarming the mixture to 45°C. and adding 1 drop of methyl iodide. Theremainder of the halide is added at a rate to maintain a temperature of43°-46°C. and the mixture is heated at 45°C. for 1 hour after completeaddition of the halide. The Grignard reagent is cooled and added to anice cooled solution of 2.615 g. (0.0117 mole) of 2-(6-carbomethoxyhexyl)2-cyclopentenone (Example 83) and 0.229 g. of Copper (I)iodide-tri-in-butylphosphine in 6 ml. of ether over 6 minutes. Themixture is stirred with ice cooling for 30 minutes and poured into 200ml. of saturated ammonium chloride. The mixture is extracted into etherand the organic phase is washed with water and saturated brine, dried(NaSO₄) and evaporated. The residual oil is heated to 80°C. for 30minutes with 80% aqueous acetic acid under an inert atmosphere. Thismixture is cooled, evaporated to dryness, and the residue is separatedby dry column chromatography on silica gel using benzene-ethyl acetate4:1 as eluent. The title compounds are isolated as oils with Δ13 trans/Δ13 cis in ratio of 10:1. Complete resolution is effected withpartition chromatography [for a description see M.J. Weiss et al.,Tetrahedron, 20, 357 (1964)] on acid-washed Celite -545 using heptane:acetonitrile (Hold Back Volume=1000 ml.); 11-deoxy-prostaglandin-E₁methyl ester is obtained in Hold Back Volume 3-5 and methyl15-hydroxy-9oxo-13-cis-prostenoate is obtained in Hold Back Volume 6-8.

EXAMPLE 733 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.243 g. (0.010 g. atom) of magnesium in 4 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 4.494 g. (0.010 mole) of 1-bromo-3-trityloxy-trans-1-octene in 4 ml.of tetrahydrofuran. Reaction is initiated by warming the mixture to65°C. and adding 1 drop of methyl iodide. The remainder of the halide isadded at a rate to maintain a temperature of 65°-70°C. and the mixtureis heated at 75°-80°C. for 30 minutes after complete addition of thehalide. The Grignard reagent is cooled and added to 2.243 g. (0.010mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone and 0.200 g. of copper(I) iodide-tri-n-butylphosphine in 6 ml. of ether and worked up withsaturated ammonium chloride solution and aqueous acetic acid in themanner of Example 121. The products are isolated as described in Example732 to yield 11- deoxy-prostaglandin E₁ methyl ester and methyl15-hydroxy-9-oxo-13-cis-prostenoate in a ratio of 2:1.

EXAMPLE 734 Preparation of 15-hydroxy-9-oxo-13-cis-prostenoic acid

Methyl 15-hydroxy-9-oxo-13-cis-prostenoic acid is treated with potassiumhydroxide in aqueous methanol and worked up as described in Example 495to yield the title compound, m.p. 71°-75°C.

EXAMPLE 735 Preparation of Prostaglandin-E₁ and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

A Grignard reagent is prepared as described in Example 732 from 0.535 g.(0.022 g. atom) of magnesium, 6.742 g. (0.015 mole) of1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 11 ml. oftetrahydrofuran at a temperature of 40°-42°C. The Grignard reagent isadded to 3.95 g. of2-(6-carbotetrahydropyranyloxyhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone(Example 95) and 0.589 g. of copper (I) iodide tri-n-butylphosphine in10 ml. of tetrahydrofuran and is worked up with ammonium chloride asdescribed in Example 732. The protecting groups are removed by treatingthe worked up material, as described in Example 121, with 320 mol ofacetic acid-water-tetrahydrofuran 2:1:1 at 45°C. and the products areisolated by chromatography on silica gel with a benzene-ethyl acetategradient and resolved via partition chromatography on acid-washed Celite545.

EXAMPLE 736 Preparation of Prostaglandin-E₁, and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

Treatment of2-(6-carbotetrahydopyranylhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone(Example 95) with the Grignard reagent prepared from1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in the presenceof Copper (I) iodide tri-n-butylphosphine complex by the proceduredescribed in Example 733 is productive of the subject compounds.

EXAMPLE 737 Preparation of 9α,15-dihydroxy-13-trans-prostenoic acid

To a solution of 433 mg. of 9-oxo-15-hydroxy-13-trans-prostenoic acid in4.5 ml. of tetrahydrofuran, stirred in an ice bath under nitrogenatmosphere, is added dropwise 3.7 ml. of 0.76M lithiumperhydro-9b-boraphenalylhydride. After 40 minutes at 0°C. there is added1.62 ml. of 3N sodium hydroxide followed by 1.62 ml. of 30% hydrogenperoxide. Ether is added and the resulting solution is acidified with 2Nhydrochloric acid. The ether layer is washed several times withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness to give the subject product as an oil.

EXAMPLES 738-893

Treatment of the 9-oxo derivatives designated in the table below withlithium perhydro-9b-boraphenalyl hydride by the procedure described inExample 737 provides the 9α,15-dihydroxy derivatives of the table.

                  TABLE 9                                                         ______________________________________                                              Starting 9-oxo-                                                         Ex-   derivative of Product 9α,15-Dihydroxy                             ample Example       Derivative                                                ______________________________________                                        738   375           9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans-prosten-                                                      oic acid                                                  739   376           9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans-pros-                                                        tenoic acid                                               740   377           9α,15-dihydroxy-2-ethyl-                                                13-trans-prostenoic                                                           acid                                                      741   378           9α,15-dihydroxy-3,3-di-                                                 methyl-13-trans-prosten-                                                      oic acid                                                  742   379           9α,15-dihydroxy-3-oxa-                                                  13-trans-prostenoic                                                           acid                                                      743   380           9α,15-dihydroxy-7-nor-                                                  13-trans-prostenoic                                                           acid                                                      744   381           9α,15-dihydroxy-2-fluoro-                                               13-trans-prostenoic acid                                  745   382           9α,15-dihydroxy-7a-homo-                                                13-trans-prostenoic acid                                  746   383           9α,15-dihydroxy-2-phenyl-                                               13-trans-prostenoic acid                                  747   384           9α,15-dihydroxy-2-methyl-                                               13-trans-prostenoic acid                                  748   385           9α,15-dihydroxy-10a-homo-                                               13-trans-prostenoic acid                                  749   386           9α,15-dihydroxy-10a-homo-                                               5,6,7-trinor-13-trans-                                                        prostenoic acid                                           750   387           9α,15-dihydroxy-10a-homo-                                               7-nor-13-trans-prosten-                                                       oic acid                                                  751   388           9α,15-dihydroxy-7a,10a-                                                 bishomo-13-trans-pros-                                                        tenoic acid                                               752   389           9α,15-dihydroxy-3-thia-                                                 13-trans-prostenoic                                                           acid                                                      753   390           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                           754   391           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                           755   392           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                           756   393           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                           757   394           9α,15-dihydroxy-5-cis,13-                                               trans-prostadienoic acid                                  758   395           9α,15-dihydroxy-20-nor-                                                 13-trans-prostenoic acid                                  759   396           9α,15-dihydroxy-20-meth-                                                yl-13-trans-prostenoic                                                        acid                                                      760   397           9α,15-dihydroxy-16-ethyl-                                               13-trans-prostenoic acid                                  761   398           9α,15-dihydroxy-16-meth-                                                yl-20-nor-13-trans-pros-                                                      tenoic acid                                               762   399           9α,15-dihydroxy-19-meth-                                                yl-13-trans, 18-prosta-                                                       dienoic acid                                              763   400           9α,15-dihydroxy-18,19-di-                                               methyl-13-trans, 18-pros-                                                     tadienoic acid                                            764   401           9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                                 765   402           9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans, 17-cis-                                                      prostadienoic acid                                        766   403           9α,15-dihydroxy-6,7-di-                                                 nor-13-trans, 17-cis-                                                         prostadienoic acid                                        767   404           9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                    768   405           9α,15-dihydroxy-2-ethyl-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                            769   406           9α,15-dihydroxy-3,3-di-                                                 methyl-13-trans, 17-cis-                                                      prostadienoic acid                                        770   407           9α,15-dihydroxy-3-oxa-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                            771   408           9α,15-dihydroxy-7-nor-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                            772   409           9α,15-dihydroxy-2-fluoro-                                               13-trans, 17-cis-pros-                                                        tadienoic acid                                            773   410           9α,15-dihydroxy-7a-homo-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                            774   411           9α,15-dihydroxy-2-phen-                                                 yl-13-trans, 17-cis-                                                          prostadienoic acid                                        775   412           9α,15-dihydroxy-2-meth-                                                 yl-13-trans, 17-cis-                                                          prostadienoic acid                                        776   413           9α,15-dihydroxy-10a-ho-                                                 mo-13-trans, 17-cis-                                                          prostadienoic acid                                        777   414           9α,15-dihydroxy-10a-ho-                                                 mo-5,6,7-trinor-13-                                                           trans, 17-cis-prostadi-                                                       enoic acid                                                778   415           9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-13-trans, 17-                                                        cis-prostadienoic acid                                    779   416           9α,15-dihydroxy-7a,10a-                                                 bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                    780   417           9α,15-dihydroxy-3-thia-                                                 13-trans, 17-cis-pros-                                                        tadienoic acid                                            781   418           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                782   419           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                783   420           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                                784   421           9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                                 785   422           9α,15-dihydroxy-5,6,7-                                                  trinor-19-isobutyl-13-                                                        trans, 18-prostadien-                                                         oic acid                                                  786   423           9α,15-dihydroxy-5,6,7-                                                  19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                     787   424           9α,15-dihydroxy-19,20-di-                                               nor-13-trans, 18-prosta-                                                      dienoic acid                                              788   425           9α,15-dihydroxy-17,20-di-                                               methyl-20-isopropenyl-13-                                                     trans-prostenoic acid                                     789   426           9α,15-dihydroxy-16-ethyl-                                               6,7,19,20-tetranor-13-                                                        trans-prostenoic acid                                     790   427           9α,15-dihydroxy-18,19-                                                  dimethyl-6,7-dinor-13-                                                        trans, 18-prostadienoic                                                       acid                                                      791   428           9α,15-dihydroxy-16-ethyl-                                               7a,7b-bishomo-13-trans-                                                       prostenoic acid                                           792   429           9α,15-dihydroxy-19-meth-                                                yl-7a,7b-bishomo-13-                                                          trans, 18-prostadienoic                                                       acid                                                      793   430           9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-13-trans-                                                         prostenoic acid                                           794   431           9α,15-dihydroxy-2,20-di-                                                ethyl-13-trans-prosten-                                                       oic acid                                                  795   432           9α,15-dihydroxy-2-ethyl-                                                16-methyl-20-nor-13-                                                          trans-prostenoic acid                                     796   433           9α,15-dihydroxy-2-ethyl-                                                18,19-dimethyl-13-                                                            trans, 18-prostadienoic                                                       acid                                                      797   434           9α,15-dihydroxy-3,3-di-                                                 methyl-18,19,20-trinor-                                                       13-trans-prostenoic                                                           acid                                                      798   435           9α,15-dihydroxy-3,3,20-                                                 trimethyl-13-trans-                                                           prostenoic acid                                           799   436           9α,15-dihydroxy-3,3,16-                                                 trimethyl-20-nor-13-                                                          trans-prostenoic acid                                     800   437           9α,15-dihydroxy-3,3-di-                                                 methyl-19-isobutyl-13-                                                        trans, 18-prostadienoic                                                       acid                                                      801   438           9α,15-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-13-                                                        trans, 17-prostadienoic                                                       acid                                                      802   439           9α,15-dihydroxy-3-oxa-20-                                               nor-13-trans-prostenoic                                                       acid                                                      803   440           9α,15-dihydroxy-3-oxa-20-                                               methyl-13-trans-prosten-                                                      oic acid                                                  804   441           9α,15-dihydroxy-3-oxa-16-                                               ethyl-13-trans-prosten-                                                       oic acid                                                  805   442           9α,15-dihydroxy-3-oxa-16-                                               methyl-20-nor-13-trans-                                                       prostenoic acid                                           806   443           9α,15-dihydroxy-3-oxa-                                                  19,20-dinor-13-trans, 17-                                                     prostadienoic acid                                        807   444           9α,15-dihydroxy-7,19,20-                                                trinor-13-trans, 17-                                                          prostadienoic acid                                        808   445           9α,15-dihydroxy-7-nor-                                                  18,19-dimethyl-13-trans,                                                      18,prostadienoic acid                                     809   446           9α,15-dihydroxy-7,18,19,-                                               20-tetranor-16-methyl-13-                                                     trans-prostenoic acid                                     810   447           9α,15-dihydroxy-2-fluoro-                                               20-nor-13-trans-prosten-                                                      oic acid                                                  811   448           9α,15-dihydroxy-2-fluoro-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                               812   449           9α,15-dihydroxy-2-fluoro-                                               16-ethyl-19,20-dinor-13-                                                      trans-prostenoic acid                                     813   450           9α,15-dihydroxy-2-fluoro-                                               16-methyl-20-nor-13-                                                          trans-prostenoic acid                                     814   451           9α,15-dihydroxy-2-fluoro-                                               19-methyl-13-trans, 18-                                                       prostadienoic acid                                        815   452           9α,15-dihydroxy-7a-homo-                                                18,19-dimethyl-13-trans,                                                      18-prostadienoic acid                                     816   453           9α,15-dihydroxy-7a-homo-                                                19,20-dinor-13-trans,                                                         17-prostadienoic acid                                     817   454           9α,15-dihydroxy-2-phenyl-                                               20-nor-13-trans-prosten-                                                      oic acid                                                  818   455           9α,15-dihydroxy-2-phenyl-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                               819   456           9α ,15-dihydroxy-2-phenyl-                                              16-ethyl-13-trans-pros-                                                       tenoic acid                                               820   484           9α,15-dihydroxy-20-nor-5-                                               cis, 13-trans-prostadi-                                                       enoic acid                                                821   485           9α,15-dihydroxy-20-meth-                                                yl-5-cis, 13-trans-pros-                                                      tadienoic acid                                            822   486           9α,15-dihydroxy-16-ethyl-                                               5-cis, 13-trans-prosta-                                                       dienoic acid                                              823   487           9α,15-dihydroxy-16-meth-                                                yl-20-nor-5-cis, 13-                                                          trans-prostadienoic                                                           acid                                                      824   488           9α,15-dihydroxy-19-meth-                                                yl-5-cis, 13-trans, 18-                                                       prostatrienoic acid                                       825   489           9α,15-dihydroxy-18,19-                                                  dimethyl-5-cis, 13-                                                           trans, 18-prostatrien-                                                        oic acid                                                  826   490           9α,15-dihydroxy-19,20-di-                                               nor-5-cis, 13-trans, 17-                                                      prostatrienoic acid                                       827   491           9α,15-dihydroxy-5-cis,-                                                 13-trans, 17-cis-prosta-                                                      trienoic acid                                             828   734           9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                           829   735           9α,11α,15-trihydroxy-13-                                          cis-prostenoic acid                                       830   615           9α,15-dihydroxy-2-ethyl-                                                prostanoic acid                                           831   616           9α,15-dihydroxy-3,3-di-                                                 methyl-prostanoic acid                                    832   617           9α,15-dihydroxy-3-oxa-                                                  prostanoic acid                                           833   618           9α,15-dihydroxy-2-fluoro-                                               prostanoic acid                                           834   619           9α,15-dihydroxy-2-phenyl-                                               prostanoic acid                                           835   620           9α,15-dihydroxy-2-meth-                                                 yl-prostanoic acid                                        836   621           9α,15-dihydroxy-3-thia-                                                 prostanoic acid                                           837   622           9α,15-dihydroxy-5-cis-                                                  prostenoic acid                                           838   623           9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-prostanoic                                                        acid                                                      839   624           9α,15-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-pros-                                                      tanoic acid                                               840   625           9α,15-dihydroxy-3-oxa-                                                  19,20-dinor-prostanoic                                                        acid                                                      841   626           9α,15-dihydroxy-2-fluoro-                                               19,20-dinor-prostanoic                                                        acid                                                      842   627           9α,15-dihydroxy-2-phenyl-                                               19,20-dinor-prostanoic                                                        acid                                                      843   628           9α,15-dihydroxy-2-meth-                                                 yl-19,20-dinor-prostan-                                                       oic acid                                                  844   629           9α,15-dihydroxy-3-thia-                                                 19,20-dinor-prostanoic                                                        acid                                                      845   630           9α,15-dihydroxy-19,20-di-                                               nor-5-cis-prostenoic acid                                 846   631           9α,15-dihydroxy-16-pros-                                                tynoic acid                                               847   632           9α,15-dihydroxy-6,7-di-                                                 nor-16-prostynoic acid                                    848   633           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-prostynoic                                                         acid                                                      849   634           9α,15-dihydroxy-2-ethyl-                                                16-prostynoic acid                                        850   635           9α,15-dihydroxy-3,3-di-                                                 methyl-16-prostynoic                                                          acid                                                      851   636           9α,15-dihydroxy-3-oxa-16-                                               prostynoic acid                                           852   637           9α,15-dihydroxy-7-nor-16-                                               prostynoic acid                                           853   638           9α,15-dihydroxy-2-fluoro-                                               16-prostynoic acid                                        854   639           9α,15-dihydroxy-7a-homo-                                                16-prostynoic acid                                        855   640           9α,15-dihydroxy-2-phenyl-                                               16-prostynoic acid                                        856   641           9α,15-dihydroxy-2-methyl-                                               16-prostynoic acid                                        857   642           9α,15-dihydroxy-3-thia-                                                 16-prostynoic acid                                        858   643           9α,15-dihydroxy-10a-ho-                                                 mo-16-prostynoic acid                                     859   644           9α,15-dihydroxy-10a-ho                                                  mo-7-nor-16-prostynoic                                                        acid                                                      860   645           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-prostynoic                                                         acid                                                      861   646           9α,15-dihydroxy-16-yne-                                                 5-cis-prostenoic acid                                     862   683           9α,15-dihydroxy-16-trans-                                               prostenoic acid                                           863   684           9α,15-dihydroxy-6,7-di-                                                 nor-16-trans-prostenoic                                                       acid                                                      864   685           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-trans-pros-                                                        tenoic acid                                               865   686           9α,15-dihydroxy-2-ethyl-                                                16-trans-prostenoic acid                                  866   687           9α,15-dihydroxy-3,3-di-                                                 methyl-16-trans-prosten-                                                      oic acid                                                  867   688           9α,15-dihydroxy-3-oxa-16-                                               trans-prostenoic acid                                     868   689           9α,15-dihydroxy-7-nor-16-                                               trans-prostenoic acid                                     869   690           9α,15-dihydroxy-2-fluoro-                                               16-trans-prostenoic acid                                  870   691           9α,15-dihydroxy-7a-homo-                                                16-trans-prostenoic acid                                  871   692           9α,15-dihydroxy-2-phenyl-                                               16-trans-prostenoic acid                                  872   693           9α,15-dihydroxy-2-methyl-                                               16-trans-prostenoic acid                                  873   694           9α,15-dihydroxy-3-thia-                                                 16-trans-prostenoic acid                                  874   695           9α,15-dihydroxy-10a-homo-                                               16-trans-prostenoic acid                                  875   696           9α,15-dihydroxy-10a-homo-                                               7-nor-16-trans-prosten-                                                       oic acid                                                  876   697           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-trans-pros-                                                        tenoic acid                                               877   698           9α,15-dihydroxy-5-cis,-                                                 16-trans-prostadienoic                                                        acid                                                      878   647           9α,15-dihydroxy-16-cis-                                                 prostenoic acid                                           879   648           9α,15-dihydroxy-6,7-di-                                                 nor-16-cis-prostenoic                                                         acid                                                      880   649           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-cis-prosten-                                                       oic acid                                                  881   650           9α,15-dihydroxy-2-ethyl-                                                16-cis-prostenoic acid                                    882   651           9α,15-dihydroxy-3,3-di-                                                 methyl-16-cis-prosten-                                                        oic acid                                                  883   652           9α,15-dihydroxy-3-oxa-                                                  16-cis-prostenoic acid                                    884   653           9α,15-dihydroxy-7-nor-                                                  16-cis-prostenoic acid                                    885   654           9α,15-dihydroxy-2-fluoro-                                               16-cis-prostenoic acid                                    886   655           9α,15-dihydroxy-7a-homo-                                                16-cis-prostenoic acid                                    887   656           9α,15-dihydroxy-2-phenyl-                                               16-cis-prostenoic acid                                    888   657           9α,15-dihydroxy-2-methyl-                                               16-cis-prostenoic acid                                    889   658           9α,15-dihydroxy-3-thia-                                                 16-cis-prostenoic acid                                    890   659           9α,15-dihydroxy-10a-ho-                                                 mo-16-cis-prostenoic                                                          acid                                                      891   660           9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-16-cis-prosten-                                                      oic acid                                                  892   661           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-cis-prosten-                                                       oic acid                                                  893   662           9α,15-dihydroxy-5-cis-                                                  16-cis-prostadienoic                                                          acid                                                      ______________________________________                                    

EXAMPLE 894 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one

Treatment of 2-cyclopentanone carboxylate (mixed methyl and ethylesters) with 2-methoxyethyl bromide by the method of Example 1 furnishesthe subject compound as an oil, b.p. 90°C. (0.1 mm).

EXAMPLE 895 Preparation of 2-(2-methoxyethyl)cyclopentan-1-one

Heating 8 g. of 2-carboalkoxy(methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one (Example 894) in 8ml. of 20% aqueous hydrochloric acid at reflux for 3.5 hours andisolating the product by the method of Example 2 furnishes the subjectcompound as an oil, b.p. 45°-50°C. (0.02 mm).

EXAMPLE 896 Preparation of 1-acetoxy-2-(2-methoxyethyl)cyclopent-1-ene

The subject compound is prepared from 2-(2-methoxyethyl)cyclopentan-1-one (Example 895) and acetic anhydride by the procedure of Example 10.The product is an oil, b.p. 60°C. (0.2 mm.)

EXAMPLE 897 Preparation of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one

The enol acetate of Example 896 is brominated and dehydrobrominated bythe method described in Example 13. The crude product is then dissolvedin methylene chloride and is added a7 -78°C. to a methylene chloridesolution containing about seven molar equivalents of boron tribromide.After 1 hour a -78°C. the solution is allowed to warm to roomtemperature and is then kept at ambient temperatures for a total ofeighteen hours. The mixture is poured into water and extracted withether. The organic phase is washed with saturated saline solution, thenwater and is dried. Evaporation of solvents leaves subject product,which is purified by distillation. The combined organic phases arewashed with ice cold 5% sodium hydroxide solution, ice cold 5%hydrochloric acid, and saturaated sodium chloride solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives apale yellow oil; λ max 5.85 μ (carbonyl group).

EXAMPLE 898 Preparation of 2-formylmethylcycopent-2-en-1-one

Chromium trioxide (0.5 mol) is added to a stirring solution of (1.2 mol)of anhydrous pyridine in 1500 ml. of anhydrous methylene chloride cooledin an ice bath. The deep red suspension is stirred for 15 minutes at0°C, and 45 minutes at ambient temperature. A solution of 01.5 mol of2-(2-hydroxyethyl)-cyclopent-2-en-1 -one (Example 897) in 50 ml. ofmethylene chloride is added, all at once, to the suspension. A blackterry deposit is formed immediately. After stirring the mixture for 25minutes at ambient temperature, the methylene chloride is decanted fromthe tarry precipitate which is then triturated several times with ether.

EXAMPLE 899 Preparation of2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one

A mixture of 0.194 g. (0.007952 mole) of sodium hydride (free of mineraloil) and 5.5 ml. of dimethylsulfoxide is heated to 70°C. until gasevolution ceases under a nitrogen atmosphere. The resulting solution iscooled below room temperature and treated with a solution of 1.400 g.(0.00316 mole) of 4-carboxybutyltriphenyl phosphonium bromide [E. J.Corey et al., J. Am. Chem. Soc., 91, 5675 (1969)] in 6 ml. ofdimethylsulfoxide. To the resulting red solution is added 0.00263 moleof 2-formylmethylcyclopent-2-en-1-one (Example 898) in 2 ml. ofdimethylsulfoxide and the mixture is stirred at room temperature for2.25 hours. The mixture is poured into ice water, sodium hydroxidesolution is added to pH 12, and the neutral materials are extracted withdiethyl ether. The basic phase is acidified with dilute hydrochloricacid and is extracted with diethyl ether. The organic phase is washedwith water and saturated brine, dried (Na₂ SO₄), and evaporated to asemicrystalline mass. The latter is triturated with hot hexane, thesolids are filtered off, and the filtrate is evaporated to yield thesubject product as an oil.

EXAMPLE 900 Preparation of2-(6-carbomethoxy-2-cis-hexenyl)-cyclopent-2-en-1-one

Treatment of 2-(6-caboxy-2-cis-hexenyl)-cyclopent-2-en-1-one (Example899) with diazomethane in the usual manner is productive of the subjectester.

EXAMPLES 901-909

Hydrogenation of 13-trans-prostenoic acids designated in the table belowby the procedure of Example 699 is productive of the prostanoic acids ofthe table.

                  TABLE 10                                                        ______________________________________                                        Ex-     Starting 13-  Product                                                 ample   trans-pro-    Prostanoic                                                      stenoic acid  Acid                                                            of Example                                                            ______________________________________                                        901     397           9-oxo-15-hydroxy-                                                             16-ethyl-pro-                                                                 stanoic acid                                            902     398           9-oxo-15-hydroxy-                                                             16-methyl-20-                                                                 nor-prostanoic                                                                acid                                                    903     400           9-oxo-15-hydroxy-                                                             18,19-dimethyl-                                                               prostanoic acid                                         904     426           9-oxo-15-hydroxy-                                                             16-ethyl-6,7,19,                                                              20-tetranor-pro-                                                              stanoic acid                                            905     428           9-oxo-15-hydroxy-                                                             16-ethyl-7a,7b-                                                               bishomo-prostan-                                                              oic acid                                                906     429           9-oxo-15-hydroxy-                                                             19-methyl-7a,7b-                                                              bishomo-prostan-                                                              oic acid                                                907     433           9-oxo-15-hydroxy-                                                             2-ethyl-18,19-                                                                dimethyl-pro-                                                                 stanoic acid                                            908     436           9-oxo-15-hydroxy-                                                             3,3,16-trimethyl-                                                             20-nor-prostanoic                                                             acid                                                    909     476           9-oxo-15-hydroxy-                                                             7a,10a-bishomo-16-                                                            methyl-20-nor-                                                                prostanoic acid                                         ______________________________________                                    

EXAMPLES 910-915

Treatment of the 9-oxo-alkyl esters designated in the table below withsodium borohydride by the procedure described in Example 257 isproductive of the corresponding 9-hydroxy derivative of the table. Theseproducts are obtained as 9α- and 9β-hydroxy epimeric mixtures.

                  TABLE 11                                                        ______________________________________                                        Ex-    Starting 9-oxo                                                                              Product                                                  ample  derivative of 9α/9β-hydroxy derivative                             Example                                                                ______________________________________                                        910    260           ethyl 9α/9β,15-dihydroxy-                                          2-ethyl-13-trans-                                                             prostenoate                                              911    261           ethyl 9α/9β,15-dihydroxy-                                          3,3-dimethyl-13-trans-                                                        prostenoate                                              912    262           ethyl 9α/9β,15-dihydroxy-                                          3-oxa-13-trans-                                                               prostenoate                                              913    266           ethyl 9α/9β,15-dihydroxy-                                          2-phenyl-13-trans-                                                            prostenoate                                              914    272           ethyl 9α/9β,15-dihydroxy-                                          3-thia-13-trans-                                                              prostenoate                                              915    284           ethyl 9α/9β,15-dihydroxy-                                          13-trans,17-cis-                                                              prostadienoate                                           ______________________________________                                    

EXAMPLES 916-921

Saponification of the ethyl esters designated in the table below by theprocedure described in Example 122 furnishes the carboxylic acids of thetable.

                  TABLE 12                                                        ______________________________________                                                               Product 9α/9β,15-di-                        Ex-     Starting ethyl hydroxy-13-trans-pro-                                  ample   ester of Example                                                                             stenoic acid                                           ______________________________________                                        916     910            9α/9β,15-dihydroxy-                                                2-ethyl-13-trans-                                                             prostenoic acid                                        917     911            9α/9β,15-dihydroxy-                                                3,,3-dimethyl-13-                                                             trans-prostenoic                                                              acid                                                   918     912            9α/9β,15-dihydroxy-                                                3-oxa-13-trans-                                                               prostenoic acid                                        919     913            9α/9β,15-dihydroxy-                                                2-phenyl-13-trans-                                                            prostenoic acid                                        920     914            9α/9β,15-dihydroxy-                                                3-thia-13-trans-                                                              prostenoic acid                                        921     915            9α/9β,15-dihydroxy-                                                13-trans,17-cis-                                                              prostadienoic acid                                     ______________________________________                                    

EXAMPLES 922-932

Treatment of the cycloalkenones of Table 13, which follows, with theGrignard reagent, prepared from1-bromo-3-triphenylmethoxy-trans-1-octene and magnesium according to theprocedure of Example 733, hydrolizing the intermediate15-O-triphenylmethyl derivatives with glacial aceticacid-tetrahydrofura-water (4:2:1) according to the procedure of Example121, and isolating the products in the manner described in Example 732is productive of the product 9-oxo-15-hydroxy-13-cis-prostenoates and9oxo-15-hydroxy-13-trans-prostenoates of the table.

                                      TABLE 13                                    __________________________________________________________________________    Example                                                                            Starting cyclopentenone                                                                    Product 15-hydroxy-13-cis-                                                                      Product 15-hydroxy-13-trans-                   Ester of Example                                                                           prostenoate ester prostenoate ester                         __________________________________________________________________________    922  23           ethyl 9-oxo-15-hydroxy-7a,7b-                                                                   ethyl 9-oxo-15-hydroxy-7a,7b-                               bishomo-13-cis-prostenoate                                                                      bishomo-13-trans-prostenoate              923  31           ethyl 9-oxo-15-hydroxy-2-ethyl-                                                                 ethyl 9-oxo-15-hydroxy-2-                                   13-cis-prostenoate                                                                              ethyl-13-trans-prostenoate                924  41           ethyl 9-oxo-15-hydroxy-3,3-di-                                                                  ethyl 9-oxo-15-hydroxy-3,3-di-                              methyl-13-cis-prostenoate                                                                       methyl 13-trans-prostenoate               925  46           ethyl 9-oxo-15-hydroxy-3-oxa-                                                                   ethyl 9-oxo-15-hydroxy-3-oxa-                               13-cis-prostenoate                                                                              13-trans-prostenoate                      926  53           ethyl 9-oxo-15-hydroxy-7-nor-                                                                   ethyl 9-oxo-15-hydroxy-7-nor-                               13-cis-prostenoate                                                                              13-trans-prostenoate                      927  70           ethyl 9-oxo-15-hydroxy-2-fluoro-                                                                ethyl 9-oxo-15-hydroxy-2-                                   13-cis-prostenoate                                                                              fluoro-13-trans-prostenoate               928  84           n-decyl 9-oxo-15-hydroxy-                                                                       n-decyl 9-oxo-15-hydroxy-                                   13-cis-prostenoate                                                                              13-trans-prostenoate                      929  99           ethyl 9-oxo-15-hydroxy-2-methyl-                                                                ethyl 9-oxo-15-hydroxy-2-                                   13-cis-prostenoate                                                                              methyl-13-trans-prostenoate               930  111          ethyl 9-oxo-15-hydroxy-10a-homo-                                                                ethyl 9-oxo-15-hydroxy-10a-                                 13-cis-prostenoate                                                                              homo-13-trans-prostenoate                 931  118          ethyl 9-oxo-15-hydroxy-3-thia-                                                                  ethyl 9-oxo-15-hydroxy-3-                                   13-cis-prostenoate                                                                              thia-13-trans-prostenoate                 932  900          methyl 9-oxo-15-hydroxy-5-                                                                      methyl 9-oxo-15-hydroxy-5-                                  cis, 13-cis-prostadienoate                                                                      cis, 13-trans-                                                                prostadienoate                            __________________________________________________________________________

EXAMPLES 933-942

Saponification of the 13-cis-prostenoate alkyl esters designated inTable 14 below by the method described in Example 122 is productive ofthe 13-cis-prostenoic acids of the Table.

                                      TABLE 14                                    __________________________________________________________________________    Example                                                                            Starting 13-cis-prostenoate                                                                   Product 13-cis-prostenoic acids                               Ester of Example                                                         __________________________________________________________________________    933  922             9-oxo-15-hydroxy-7a,7b-bishomo-13-                                            cis-prostenoic acid                                      934  923             9-oxo-15-hydroxy-2-ethyl-13-cis-                                              prostenoic acid                                          935  924             9-oxo-15-hydroxy-3,3-dimethyl-13-cis                                          prostenoic acid                                          936  925             9-oxo-15-hydroxy-3-oxa-13-cis-prostenoic acid            937  926             9-oxo-15-hydroxy-7-nor-13-cis-prostenoic acid            938  927             9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoic acid         939  929             9-oxo-15-hydroxy-2-methyl-13-cis-prostenoic acid         940  930             9-oxo-15-hydroxy-10a-homo-13-cis-prostenoic acid         941  931             9-oxo-15-hydroxy-3-thia-13-cis-prostenoic acid           942  932             9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoic             __________________________________________________________________________                         acid                                                 

EXAMPLES 943-954

Treatment of the 9-oxo-13-cis-prostenoic acids and esters of Table 15below with lithium perhydro-9b-boraphenalyl hydride by the proceduredescribed in Example 737 furnishes the 9α,15-dihydroxy-13-cis-prostenoicacids and esters of the table.

                                      TABLE 15                                    __________________________________________________________________________    Example                                                                            Starting 9-oxo-13-cis-                                                                     Product 9α,15-hydroxy-13-cis-prostenoic acid and                        esters                                                           prostenoic derivative                                                         of Example                                                               __________________________________________________________________________    943  933          9,15-dihydroxy-7a,7b-bishomo-13-cis-prostenoic acid         944  934          9,15-dihydroxy-2-ethyl-13-cis-prostenoic acid               945  935          9,15-dihydroxy-3,3-dimethyl-13-cis-prostenoic acid          946  936          9,15-dihydroxy-3-oxa-13-cis-prostenoic acid                 947  937          9,15-dihydroxy-7-nor-13-cis-prostenoic acid                 948  938          9,15-dihydroxy-2-fluoro-13-cis-prostenoic acid              949  939          9,15-dihydroxy-2-methyl-13-cis-prostenoic acid              950  940          9,15-dihydroxy-10a-homo-13-cis-prostenoic acid              951  941          9,15-dihydroxy-3-thia-13-cis-prostenoic acid                952  942          9,15-dihydroxy-5-cis,-13-cis-prostadienoic acid             953  932          methyl 9,15-dihydroxy-5-cis, 13-cis-prostadienoate          954  928          n-decyl 9,15-dihydroxy-13-cis-prostenoate                   __________________________________________________________________________

EXAMPLE 955 Preparation of 1-iodo-trans-1-octen-3-ol

A solution of 78.2 g. (0.310 moles) of 1-iodo-trans-1-octen-3-one(Example 724) in 150 ml. of absolute ethanol is added dropwise over 2hours to a slurry of 6.49 g. (0.172 moles) of sodium borohydride in 50ml. of absolute ethanol cooled in an ice bath. After the addition iscomplete, the mixture is stirred for 2 hours with ice cooling and isthen poured into 1 l. of water. The mixture is extracted into benzeneand the organic phase is washed with saturated brine, dried (Na₂ SO₄)and evaporated. The resulting oil is dissolved into 400 ml. of absoluteethanol and treated with 5 mole percent of p-carboxyphenylhydrazine at70°C. for 1.5 hours to remove residual ketone. The mixture is cooled andevaporated and the residue is dissolved into 400 ml. of ether and isfiltered. The filtrate is washed with dilute sodium bicarbonate solutionand saturated brine, dried (Na₂ SO₄), and evaporated to an oil. This oilchromatographyed upon 2 Kg. of Florisil packed in hexane and the productis obtained upon elution with benzene Distillation of the product yieldsa colorless oil, b.p. 74°-76°C. (0.005 tor.).

EXAMPLE 956 Preparation of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene

A mixture of 14.92 g. (0.0588 mole) of 1-iodo-trans-1-octen-3-ol(Example 955) and 18.2 g. (0.0588 mole) of p-anisyldiphenylmethylchloride in 165 ml. of dry pyridine is heated at 60°C. for 18 hoursunder an inert atmosphere. The mixture is cooled and the solvent isevaporated in vacuo. The residue is partitioned between ether and water,and the organic phase is washed with water and saturated brine, dried(MgSO₄), and evaporated. The residue is chromatographed upon 300 g. ofFlorisil packed in hexane and the product is eluted with hexane and 4:1hexane-benzene the yield a colorless oil.

EXAMPLE 957 Preparation of methyl esters of dl-11-deoxyprostaglandin-E₁and dl-11-deoxy-15-epi-prostaglandin E₁

To a solution of 6.030 g. (0.01215 mole) of1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 8 ml. oftoluene cooled to -78°C. under an inert atmosphere is added 5.2 ml. of a2.34 M solution of n-butyllithium in hexane. The resulting solution isallowed to warm to -40°C. and is maintained at this temperature for 1hour. To the solution containing3-triphenylmethoxy-trans-1-octenyllithium is then added 5.0 ml. of a2.44 M (0.0122 mole) solution of trimethylaluminum in heptane and themixture is allowed to warm to -10°C. The mixture containing lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate is then cooled to-78°C. and to it is added a solution of 2.725 g. (0.01215 mole) of2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) dissolved in 10ml. of diethyl ether. The mixture is allowed to warm to room temperatureand is stirred at ambient temperature for 18 hours. The mixture is thenpoured onto ice and diluted hydrochloric acid and is extracted intoether. The organic phase is washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to yield a colorless oil. This oil is heatedwith 100 ml. of 80% aqueous acetic acid at 80°C. for 1 hour under aninert atmosphere. The resulting mixture is cooled and evaporated invacuo to dryness with 100 ml. of xylene to yield an oil. This oil isdry-column-chromatographed upon 400 g. of silica gel using 4:1benzene-ethyl acetate as eluent to yield a total of 2.59 g. ofdl-11-deoxyprostaglandin E₁ and dl-11-deoxy-15-epi-prostaglandin E₁methyl esters.

EXAMPLE 958 Preparation of4-(trimethylsiloxy)-2-(6-carbotrimethylsiloxyhexyl)cyclopent-2-en-1-one

To a solution of 5 g. of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one (Example 94) in 10 ml.of dry N,N-dimethylformamide is added 5.4 g. of trimethylsilyl chloridein a nitrogen atmosphre. To the resulting solution cooled in a tap waterbath is added 5.05 g. of triethylamine in 10 ml. ofN,N-dimethylformamide dropwise. The resulting mixture is stirred at60°C. in a oil-bath for 2 hours, then at ambient temperatures for 18hours. Triethylamine hydrochloride is removed by filtration and thefiltrate is taken to dryness. The residual oil is distilled to give 2.6g. of product, b.p. 156°-157°C. (0.07 mm.).

EXAMPLE 958A Preparation of4-(dimethylisopropylsiloxy)-2-(6-carbodimethylisopropylsiloxyhexyl)cyclopent-2-en-1-one

Treatment of 1 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-onein 2 ml. of dry N,N-dimethylformamide containing 1.81 g. ofdimethylisopropylsilyl chloride [E. J. C. rey, R. K. Varma, J. Amer.Chem. Soc., 93, 7320 (1971)] 1.57 g. of triethylamine in 2 ml. ofN,N-dimethylformamide in the manner described in Example 958 gives 1.45g. of product after two evaporations with toluene.

EXAMPLE 959 Preparation of4-(dimethyl-t-butylsiloxy)-2-(6-carbodimethyl-t-butylsiloxyhexyl)cyclopent-2-en-1-one

To a 0°C. solution of 2.0 gm. (8.55 mole) 4-hydroxy-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 94) and 3.65 gm. (54 mole)of imidazole in 5 ml. of dimethylformamide is added a slurry consistingof 4.07 gm. (27 mole) of dimethyl-t-butyl chlorosilane in 5 ml. ofdimethylformamide. The slurry is rinsed in with an additional 1 ml. ofdimethylformamide. The ice-bath is removed and the solution is stirredat 37°C. for 4 hours. The solution is then poured into 140 ml. of waterand the aqueous solution is extracted twice with 70 ml. of isomerichexanes. The organic layers are combined, dried with magnesium sulfatean concentrated in vacuo to an oil. Toluene (50 ml.) is added twice andevaporated in vacuo to remove unwanted low boiling impurities.

The residue is maintained under active vacuum overnight to give 3.38 gm.(7.45 mole) of an oil, that shows no hydroxyl or carboxyl absorption inthe infrared. ν max: 1720 cm.sup.⁻¹ (unsaturated ketone and silylester), 840, 815, 795, 780 cm.sup.⁻¹ (silyl ether and silyl ester).

EXAMPLE 960 Preparation of dl-prostaglandin E₁ and dl-epi-prostaglandinE₁

To a solution of 4.790 g. (0.0091 mole) of3-(p-anisyldiphenylmethoxy)-trans-1-iodo-1-octene (Example 956) in 5 ml.of toluene cooled to -78°C. under an inert atmosphere is added 3.9 ml.of 2.34 M n-butyllithium in hexane. The resulting solution is warmed to-40°C. and is maintained at this temperature for 1 hour. To the solutioncontaining 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium is thenadded 3.6 ml. of a 2.44 M solution of trimethylaluminum in heptane andthe mixture is allowed to warm to 0°C. The solution containing lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate is thenadded to a solution of 3.30 g. (0.00726 mole) of 2-(6-carbo-t-butyldimethylsiloxyhexyl)-4-(t-butyldimethylsiloxy)-2-cyclopentenone(Example 959) dissolved in 10 ml. of ether cooled to -45°C. under aninert atmosphere. The resulting solution is allowed to warm to roomtemperature and is stirred at ambient temperatures for 17 hours. Thesolution is then poured onto a mixture of 5 ml. of concentratedhydrochloric acid and 150 g. of ice. This mixture is stirred until theice melts and is extracted into ether. The organic phase is washed withice cold water and cold saturated brine, dried (Na₂ SO₄), and isevaporated (<37°C.) in vacuo. The resulting oil is then heated to 38°C.for 23 hours under an inert atmosphere with 100 ml. of 3:1:1 (V:V:V)acetic acid-tetrahydrofuran-water. The mixture is then evaporated with150 ml. of xylene in vacuo (<38°C.) to yield an oil. Chromatography ofthis oil upon 115 g. of Silic AR CC-4 (Mallinckrodt) using abenzene-ethyl acetate gradient as eluent yields dl-prostaglandin E₁,m.p. 108°-112° (from ethyl acetate) and dl-15-epi-prostaglandin E₁.

EXAMPLE 961 Preparation of 3-triphenylmethoxy-trans-1-octenyllithium

To a solution of 4.96 g. of 1-iodo-3-triphenylmethoxy-trans-1-octene(Example 730) in 10 ml. of toluene cooled to -78°C. is added under aninert atmosphere 1 molar equivalent of n-butyllithium dissolved inhexane. The reaction mixture is allowed to warm -40°C. and is thenmaintained at that temperature for 1 hour to yield a hydrocarbonsolution of 3-triphenylmethoxy-trans-1-octenyllithium.

EXAMPLE 962 Preparation of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

To a solution of 5.26 g. of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene (Example 956) in 10ml. of toluene, cooled to -78°C., is added under an inert atmosphere 1molar equivalent of n-butyllithium dissolved in hexane. The reactionmixture is allowed to warm to -40°C. and is maintained at thattemperature for 1 hour to yield a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium.

EXAMPLE 963 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40°C. is added under an inert atmosphere 1molar equivalent of trimethylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 964 Preparation of lithium[3-p-anisyldiphenylmethoxy)-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooledto -40°C. is added under an inert atmosphere 1 molar equivalent oftrimethylaluminum dissolved in hexane to yield a hydrocarbon solution ofthe title compound.

EXAMPLE 965 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-propylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40°C. is added under an inert atmosphere 1molar equivalent of tri-n-propylaluminum dissolved in hexane to yield ahydrocarbon solution of the title compound.

EXAMPLE 966 Preparation of lithium[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-tri-n-hexylalanate

To a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooledto -40°C. is added under an inert atmosphere 1 molar equivalent totri-n-hexylaluminum dissolved in heptane to yield a hydrocarbon solutionof the title compound.

EXAMPLE 967 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-decylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40°C. is added under an inert atmosphere 1molar equivalent of tri-n-decylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 968 Preparation of lithiumdi-(3-triphenylmethoxy-trans-1-octenyl)-dimethylalanate

To a hydrocarbon solution of dimethylaluminum chloride cooled to -78°C.is added under an inert atmosphere 2 molar equivalents of3-triphenylmethoxy-trans-1octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0°C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 969 Preparation of lithiumdi-[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-diethylalanate

To a hexane solution of diethylaluminum chloride cooled to -78°C. isadded under an inert atmosphere 2 molar equivalents of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane solvent. The mixture is allowed to warm to0°C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 970 Preparation of lithiumtri-(3-triphenylmethoxy-trans-1-octenyl)-ethylalanate

To a hydrocarbon solution of ethylaluminum dichloride cooled to -78°C.is added under an inert atmosphere 3 molar equivalents of3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0°C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 971 Preparation of lithiumtetra-(3-triphenylmethoxy-trans-1-octenyl)alanate

Tp a well stirred mixture of anhydrous aluminum chloride and hexanecooled to -78°C. is added under an inert atmosphere 4 molar equivalentsof 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane The mixture is allowed to warm to 0°C. to yield the titlecompound.

EXAMPLE 972 Preparation of lithiumtetra-(3-p-anisyldiphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexanecooled to 78°C. is added under an inert atmosphere 4 molar equivalentsof 3-p-anisyldiphenylmethoxy-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane. The mixture is allowed to warm to 0°C. toyield the title compound.

EXAMPLES 973-981

Substitution of lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate in Example 957 withthe lithium alanates of Examples 964, 965, 966, 967, 968, 969, 970, 971or 972 is productive of the methyl esters of d,1-11-deoxy-prostaglandinE₁ and d,11-deoxy-15-epi -prostaglandin E₁.

EXAMPLES 982-990

Substitution of lithium trimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate of Example 960 withthe lithium alanates of Examples 965, 966, 967, 968, 969, 970, 971 or972 is productive of d,1-prostaglandin-E₁ and d,1 -15-epi-prostaglandinE₁.

EXAMPLE 991 Preparation of hexanoyl bromide

A mixture of 300 g. of hexanoic acid and 260 g. of phosphorus tribromideis heated at 80°C. for 1.5 hours with stirring and protection frommoisture. The mixture is cooled and the upper phase is decanted into adistilling flask. Distillation of this material yields 400 g. of thecolorless acid bromide, b.p. 51°-53°C. (10 torr.).

EXAMPLE 992 Preparation of 1-bromo-trans-1-octen-3-one

A mixture of 300 g. of aluminum bromide and 250 ml. of1,2-dibromoethane, cooled in an ice bath and protected from moisture, issaturated with acetylene. To the mixture is added with ice cooling 150g. of hexanoyl bromide (Example 991) over a period of 20 minutes and theresulting mixture is treated with acetylene until gas uptake ceases. Thereaction mixture is poured onto 500 ml. of saturated brine and 500 g. ofice. The resulting mixture is extracted twice with 500 ml. of ether. Thecombined organic extracts are washed twice with 500 ml. of saturatedbrine and dried with anhydrous sodium sulfate. To the organic phase isadded 5 g. of hydroquinone and the solvent is evaporated in vacuo toyield the crude 1-bromo-trans-1-octen-3-one.

EXAMPLE 993 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 20 g. of sodium borohydride in 800 ml. ofanhydrous ethanol is added 160 g. of crude 1-bromo-trans-1-octen-3-one(Example 992) over a period of 0.5 hour. The mixture is stirred for 2hours with ice cooling and is then partitioned between ice water andbenzene. The organic phase is washed with water and saturated brine,dried (Na₂ SO₄), and evaporated to an oil. Distillation gives theproduct as an oil, b.p. 66°-68°C. (0.025 torr.).

EXAMPLE 994 Preparation of 4,4-dimethyl-1-octyn-3-ol

To a solution of 20.2 g. (0.220 mole) of lithiumacetylide-ethylenediamine complex in 100 ml. of dry dimethylsulfoxide isadded 25.6 g. (0.200 mole) of 2,2-dimethyl-1-hexanal, prepared accordingto the procedure of G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85,2178 (1963), in 25 ml. of dimethylsulfoxide at a rate to maintain atemperature of 25°C. (cooling). The mixture is then maintained at 25°C.for 2 hours and is poured onto ice and excess hydrochloric acid. Themixture is extracted with ether and the organic phase is washed withwater and saturated brine, dried (Na₂ SO₄), and evaporated to an oil.Distillation in vacuo yields the product as a colorless oil.

EXAMPLE 995 Preparation of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne

To a solution of 23.1 g. (0.150 mole) of 4,4-dimethyl-1-octyn-3-ol(Example 994) in 126 g. of freshly distilled dihydropyran is added 1drop of phosphorus oxychloride and the solution is maintained at ambienttemperature in a tightly stoppered flask for 20 hours. Five drops oftriethylamine are then added and the mixture is evaporated in vacuo toan oil. The oil is chromatographed on 600 g. of silica gel and theproduct is eluted with 5% ethyl acetate in benzene yielding a colorlessoil.

EXAMPLE 996 Preparation of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol

To 233 ml. of a 0.43M solution of disiamylborane in diglyme cooled to0°C. under an inert atmosphere is added 23.8 g. (0.100 mole)4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995). The mixtureis allowed to come to room temperature and is stirred at ambienttemperature for 3 hours. The solution is cooled to 0°C. and 22.5 g.(0.30 mole) of triethylamine oxide is added portionwise such that thetemperature is maintained at 0°-5°C. The mixture is stirred at 0°C. for1 hour and is then poured into 150 ml. of 1 N sodium hydroxide followedimmediately by a solution of 25.4 g. (0.100 mole) of iodine in 60 ml. oftetrahydrofuran. The mixture is stirred at ambient temperatures for 0.5hour and poured into 500 ml. of water. The mixture is decolorized byaddition of sodium thiosulfate solution and is extracted into ether. Theorganic phase is washed with water and the solvent is removed in vacuo.The residue is stirred at room temperature for 20 hours with 900 ml.3:1:1 tetrahydrofuran-acetic acid-water. The solution is evaporated invacuo and the residue is chromatographed on silica gel in benzene using10-20% ethylacetate in benzene.

EXAMPLE 997 Preparation of4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 11.2 g. (0.0396 mole) of4,4-dimethyl-1-iodo-trans-1-octen-3-ol (Example 996) with 12.8 g. oftriphenylmethyl bromide in 50 ml. of pyridine and purification onFlorisil, all as described in Example 728 gives the title compound.

EXAMPLE 998 Preparation of 5,5-dimethyl-1-octyn-3-ol

Treatment of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediamecomplex in 100 ml. of dimethylsulfoxide with 25.6 g. (0.200 mole) of3,3-dimethylhexanal [prepared according to the procedure of A. W.Burgstahler, J. Amer. Chem. Soc., 82, 4681 (1960)] and distillation ofthe product, all as described in Example 994 yields the title compound.

EXAMPLE 999 Preparation of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne

Treatment of 23.1 g. (0.150 mole) of 5,5-dimethyl---octyn-3-ol (Example998) with 126 g. of dihydropyran and 1 drop of phosphorus oxychloride asdescribed in Example 995 gives the title compound.

EXAMPLE 1000 Preparation of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol

Treatment of 23.8 g. (0.100 mole) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) successivelywith 233 ml. of 0.43 M disiamylborane in diglyme, 22.5 g. oftrimethylamine oxide, 150 ml. of 1 N sodium hydroxide, 25.4 g. ofiodine, and 900 ml. of 3:1:1 tetrahydrofuran-acetic acid-water asdescribed in Example 996 gives the title compound.

EXAMPLE 1001 Preparation of5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 6.0 g. of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol (Example1000) with 6.9 g. of triphenylmethyl bromide in 30 ml. of pyridine andpurification on Florisil, all as described in Example 728 gives thetitle compound.

EXAMPLE 1002 Preparation of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 997) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1003 Preparation of5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 1001) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1004 Preparation of lithium(4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 963 from a hydrocarbon solution of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1002)and trimethylaluminum.

EXAMPLE 1005 Preparation of lithium(5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

A hydrocarbon solution of the subject alanate is prepared from ahydrocarbon solution of 5,5-dimethyl-3-triphenylmethoxy-trans-1octenyllithium (Example 1003) and trimethylaluminum according to the procedureof Example 963.

EXAMPLES 1006-1031

Treatment of the cycloalkenones of Table 16 which follows with theindicated alanates according to the procedure of Example 957 providesthe product 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoates ofthe table. The intermediate corresponding 15-0-triphenylmethylderivatives are obtained prior to treatment with aqueous acetic acid.

                  TABLE 16                                                        ______________________________________                                        Exam-  Starting cyclo-                                                                             Product from reaction with                               ple    alkenone of   lithium (4,4-Dimethyl-3-                                        Example       triphenylmethoxy-trans-1-                                                     octenyl)trimethylalanate                                                      (Example 1004)                                           ______________________________________                                        1006   13            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-13-trans-pro-                                                     stenoate                                                 1007   23            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                     1008   31            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                        1009   41            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                     1010   46            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-oxa-13-trans-                                                   prostenoate                                              1011   53            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-7-nor-13-trans-                                                   prostenoate                                              1012   70            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                        1013   84            n-decyl 9-oxo-15-hydroxy-                                                     16,16-dimethyl-13-trans-                                                      prostenoate                                              1014   99            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-methyl-13-                                                      trans-prostenoate                                        1015    111          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-10a-homo-13-                                                      trans-prostenoate                                        1016    118          ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-thia-13-trans-                                                  prostenoate                                              1017    900          methyl 9-oxo-15-hydroxy-16,-                                                  16-dimethyl-5-cis,13-trans-                                                   prostadienoate                                           1018   79            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                        ______________________________________                                        Exam-  Starting cyclo-                                                                             Product from reaction with                               ple    alkenone of   lithium (5,5-Dimethyl-3-                                        Example       triphenylmethoxy-trans-1-                                                     octenyl)trimethylalanate                                                      (Example 1005)                                           ______________________________________                                        1019   13            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-13-trans-pro-                                                     stenoate                                                 1020   23            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                     1021   31            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                        1022   41            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                     1023   46            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-oxa-13-trans-                                                   prostenoate                                              1024   53            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7-nor-13-trans-                                                   prostenoate                                              1025   70            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                        1026   84            n-decyl-9-oxo-15-hydroxy-                                                     17,17-dimethyl-13-trans-                                                      prostenoate                                              1027   99            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-methyl-13-                                                      trans-prostenoate                                        1028    111          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-10a-homo-13-                                                      trans-prostenoate                                        1029    118          ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-thia-13-trans-                                                  prostenoate                                              1030    900          methyl 9-oxo-15-hydroxy-                                                      17,17-dimethyl-5-cis,13-                                                      trans-prostadienoate-1031 79 ethyl                                            9-oxo-15-hydroxy-17,-                                                         17-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                        ______________________________________                                    

EXAMPLES 1032-1055

Saponification of the 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoate alkyl esters of Table 17 below by the method ofExample 122 provides the corresponding prostenoic acids of the Table.

                  TABLE 17                                                        ______________________________________                                        Exam-  Starting alkyl                                                                             Product 16,16-dimethyl or                                 ple    ester of     17,17-dimethyl-9-oxo-15-                                         Example      hydroxy-13-trans-proste-                                                      noic acid                                                 ______________________________________                                        1032   1006         9-oxo-15-hydroxy-16,16-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                      1033   1007         9-oxo-15-hydroxy-16,16-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                     1034   1008         9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                           1035   1009         9-oxo-15-hydroxy-16,16-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                     1036   1010         9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                              1037   1011         9-oxo-15-hydroxy-16,16-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                              1038   1012         9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                           1039   1014         9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                           1040   1015         9-oxo-15-hydroxy-16,16-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                           1041   1016         9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-thia-13-trans-                                                       prostenoic acid                                           1042   1017         9-oxo-15-hydroxy-16,16-di-                                                    methyl-5-cis,13-trans-pro-                                                    stadienoic acid                                           1043   1018         9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-phenyl-13-trans-                                                     prostenoic acid                                           1044   1019         9-oxo-15-hydroxy-17,17-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                      1045   1020         9-oxo-15-hydroxy-17,17-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                     1046   1021         9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                           1047   1022         9-oxo-15-hydroxy-17,17-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                     1048   1023         9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                              1049   1024         9-oxo-15-hydroxy-17,17-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                              1050   1025         9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                           1051   1027         9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                           1052   1028         9-oxo-15-hydroxy-17,17-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                           1053   1029         9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-thia-13-trans-pro-                                                   stenoic acid                                              1054   1030         9-oxo-15-hydroxy-17,17-di-                                                    methyl-5-cis,13-trans-pro-                                                    stadienoic acid                                           1055   1031         9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-phenyl-13-trans-                                                     prostenoic acid                                           ______________________________________                                    

EXAMPLES 1056-1081

Treatment of the 9-oxo- acids and esters of Table 18 below with lithiumperhydro-9b-boraphenalyl hydride by the procedure of Example 737provides the 9α,15-dihydroxy-16,16-dimethyl of17,17-dimethyl-13-trans-prostenoic acid of the Table.

                  TABLE 18                                                        ______________________________________                                        Exam-  Starting 9-oxo                                                                              Product 9α-15-Dihydroxy-16,-                       ple    derivative of 16-dimethyl or 17,17-di-                                        Example       methyl-13-trans-prostenoic                                                    acids or esters                                          ______________________________________                                        1056   1032          9α,15-dihydroxy-16,16-di-                                               methyl-13-trans-prostenoic                                                    acid                                                     1057   1033          9α,15-dihydroxy-16,16-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                    1058   1034          9α,15-dihydroxy-16,16-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                          1059   1035          9α,15-dihydroxy-16,16-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                    1060   1036          9α,15-dihydroxy-16,16-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                             1061   1037          9α,15-dihydroxy-16,16-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                             1062   1038          9α,15-dihydroxy-16,16-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                          1063   1013          n-decyl 9α,15-dihydroxy-16,-                                            16-dimethyl-13-trans-proste-                                                  noate                                                    1064   1039          9α,15-dihydroxy-16,16-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                          1065   1040          9α,15-dihydroxy-16,16-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                          1066   1041          9α,15-dihydroxy-16,16-di-                                               methyl-3-thia-13-trans-pro-                                                   stenoic acid                                             1067   1042          9α,15-dihydroxy-16,16-di-                                               methyl-5-cis,13-trans-                                                        prostadienoic acid                                       1068   1043          9α,15-dihydroxy-16,16-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                          1069   1044          9α,15-dihydroxy-17,17-di-                                               methyl-13-trans-prostenoic                                                    acid                                                     1070   1045          9α,15-dihydroxy-17,17-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                    1071   1046          9α,15-dihydroxy-17,17-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                          1072   1047          9α,15-dihydroxy-17,17-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                    1073   1048          9α,15-dihydroxy-17,17-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                             1074   1049          9α,15-dihydroxy-17,17-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                             1075   1050          9α,15-dihydroxy-17,17-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                          1076   1026          n-decyl 9α,15-dihydroxy-                                                17,17-dimethyl-13-trans-                                                      prostenoate                                              1077   1051          9α,15-dihydroxy-17,17-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                          1078   1052          9α,15-dihydroxy-17,17-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                          1079   1053          9α,15-dihydroxy-17,17-di-                                               methyl-3-thia-13-trans-                                                       prostenoic acid                                          1080   1054          9α,15-dihydroxy-17,17-di-                                               methyl 5-cis,13-trans-pro-                                                    stadienoic acid                                          1081   1055          9α,15-dihydroxy-17,17-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                          ______________________________________                                    

EXAMPLE 1082

A solution of methyl 9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostatrienoate (Example 374) in tetrahydrofuran isadded to 1.1 equivalent of lithium perhydro-9b-boraphenyalyl hydride intetrahydrofuran at -78°C. After 30 minutes equal volumes of 5% aqueoussodium carbonate and 30% aqueous hydrogen peroxide is added, and thesolution is stirred 15 minutes. The solution is diluted with water andextracted with ether. The organic phase is dried (magnesium sulfate) andconcentrated in vacuo to give methyl9α,15α-dihydroxy-5-cis,13-trans,17-cis-prostatrienoate, contaminatedwith methyl 9β,15α-dihydroxy-5cis,13trans,17cis-prostatienoate. Thecrude mixture of esters is dissolved in methylene chloride and added toa refluxing solution of 1.2 equivalents of2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in methylene chloride. After5 hours, the solution is cooled and filtered. The filtrate is dilutedwith two volumes of ether, extracted with 5% aqueous sodium carbonateand dried with magnesium sulfate. The solution is concentrated in vacuoto give methyl 9α -hydroxy-15-oxo-5cis-13-trans, 17cis-prostatrienoateand 9β-hydroxy-15-oxo-5cis, 13trans,17cis-prostatrienoate. The crudematerial is dissolved in benzene and 1.2 equivalents each oftriethylamine and trimethylsilyl chloride is added. The triethylaminehydrochloride is removed by filtration and the solution is concentratedin vacuo to give methyl9α-trimethylsiloxy-15-keto-5cis,13trans,17cis-prostatrienoate and thecorresponding 9β-trimethylsiloxy derivative.

The siloxy derivatives are dissolved in ether at 0°C. and 1.05equivalents of methyl magnesium bromide in ether is added. After thereaction is complete, the solution is poured into saturated aqueousammonium chloride and extracted with ether. The ether is dried andconcentrated in vacuo to give methyl9α-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl9α-trimethylsiloxy-15β-hydroxy-15α-methyl-5cis,13trans,17-cis-prostatrienoate,methyl9β-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl 9β-trimethylsiloxy-15β-hydroxy-15α-methyl 5cis,13trans,17-'cis-prostatrienoate. Hydrolysis of the siloxy functions of each in asolution of methanol, water and acetic acid (approximately 10:1:1, 3hours ambient temperatures) and gives methyl9α,15α-dihydroxy-15β-methyl-5cis-13trans,17cis-prostatrienoate, methyl9α,15α-dihydroxy-15α-methyl-5cis,13trans, 17cis-prostatrienoate, methyl9β,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate andmethyl 9β,15β-dihydroxy-15α-methyl-5-cis,13trans,17cis-prostatrienoateseparated by dry column chromatography and further purified by partitionchromatography saponification (method of Example 122) of each componentin 50% aqueous methanol with potassium hydroxide gives the correspondingfree acids.

Treatment of a solution of methyl9α,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate inmethylene chloride with Collins reagent (CrO₃ -pyridine in methylenechloride) gives methyl9-oxo-15α-hydroxy-15β-methyl-5cis,13-trans,17cis-prostatrienoate,saponification of which (method of Example 122) gives9-oxo-15α-hydroxy-15β-methyl-5cis,13trans, 17cis-prostatrienoate acid.

Similar treatment of the 15β-hydroxy esters gives methyl9-oxo-15β-hydroxy- 15α-methyl-5cis,13trans, 17cis-prostatrienoate whichgives 9-oxo-15β-hydroxy-15α-methyl-5-cis,13trans,17cis-prostatrienoicacid after saponification.

EXAMPLES 1083-1101

Treatment of the 9-oxo15-hydroxy prostenoic esters of Table 18 A belowby the sequence of reactions described in Example 1082 is productive ofthe 9α,15-di-hydroxy-15-methyl and the 9-oxo-15-hydroxy-15-methylproducts of the table. Also prepared in the course of these reactionsequences are the ethyl (methyl for Example 1101) esters correspondingto the products of the table, the 9β-hydroxy derivatives correspondingto the listed 9α-hydroxy derivatives and their ethyl esters, the 15-ketoderivatives of the 9α- and 9β-hydroxy compounds corresponding to the9-oxo starting compounds, and the 9α- or 9β-trimethyl-silyloxy ethylesters of the 15-keto and 15-hydroxy-15-methyl compounds. In all casesboth the 15αhydroxy-15β-methyl and the 15β-hydroxy-15α-methyl productsand intermediates are obtained. These epimers are separable bychromatographic procedures.

                  TABLE 18A                                                       ______________________________________                                               Starting 9-oxo-                                                        Ex-    15-hydroxy-ester                                                                             Product 15-hydroxy-                                     ample  of Example     15-methyl derivative                                    ______________________________________                                        1083   260            9-oxo-15-methyl-15-                                                           hydroxy-2-ethyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-ethyl-13-                                                         trans-prostenoic acid                                   1084   261            9-oxo-15-hydroxy-15-                                                          methyl-3,3-dimethyl-                                                          13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            3,3-dimethyl-13-trans-                                                        prostenoic acid                                         1085   262            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans-                                                        prostenoic acid and                                                           9α,15-dihydroxy-15-                                                     methyl-3-oxa-13-trans-                                                        prostenoic acid                                         1086   264            9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-fluoro-                                                           13-trans-prostenoic                                                           acid                                                    1087   266            9-oxo-15-hydroxy-15-                                                          methyl-2-phenyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-phenyl-                                                           13-trans-prostenoic                                                           acid                                                    1088   267            9-oxo-15-hydroxy-15-                                                          methyl-2-methyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-methyl-                                                           13-trans-prostenoic                                                           acid                                                    1089   268            9-oxo-15-hydroxy-15-                                                          methyl-10a-homo-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-10a-homo-                                                           13-trans-prostenoic                                                           acid                                                    1090   272            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-                                                             trans-prostenoic acid                                                         and 9α ,15-dihydroxy-                                                   15-methyl-3-thia-13-                                                          trans-prostenoic acid                                   1091   362            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-20-                                                             methyl-13-trans-pro-                                                          stenoic acid and 9α,15-                                                 dihydroxy-15-methyl-3-                                                        thia-20-methyl-13-                                                            trans-prostenoic acid                                   1092   343            9-oxo-15-hydroxy-15-                                                          methyl-2,20-dimethyl-                                                         13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            2,20-dimethyl-13-                                                             trans, prostenoic acid                                  1093   323            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-20-methyl-                                                       13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-3-                                                          oxa-20-methyl-13-                                                             trans-prostenoic acid                                   1094   284            9-oxo-15-hydroxy-15-                                                          methyl-13-trans, 17-                                                          cis-prostadienoic acid                                                        and 9α,15-dihydroxy-15-                                                 methyl-13-trans,17-                                                           cis-prostadienoic acid                                  1095   287            9-oxo-15-hydroxy-15-                                                          methyl-7a,7b-bishomo-                                                         13-trans, 17-cis-pro-                                                         stadienoic acid and 9a,                                                       15-dihydroxy-15-methyl-                                                       7a,7b-bishomo-13-                                                             trans, 17-cis-prosta-                                                         dienoic acid                                            1096   290            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans,                                                        17-cis-prostadienoic                                                          acid and 9a,15-dihydro-                                                       xy-15-methyl-3-oxa-13-                                                        trans, 17-cis-prosta-                                                         dienoic acid                                            1097   291            9-oxo-15-hydroxy-15-                                                          methyl-7-nor-13-trans,                                                        17-cis-prostadienoic                                                          acid and 9α,15-di-                                                      hydroxy-15-methyl-7-                                                          nor-13-trans, 17-cis-                                                         prostadienoic acid                                      1098   292            9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans, 17-cis-prosta-                                                         dienoic acid and 9α,                                                    15-dihydroxy-15-methyl-                                                       2-fluoro-13-trans,                                                            17-cis-prostadienoic                                                          acid                                                    1099   293            9-oxo-15-hydroxy-15-                                                          methyl-7a-homo-13-                                                            trans, 17-cis-prosta-                                                         dienoic acid and 9α,15-                                                 dihydroxy-15-methyl-7a-                                                       homo-13-trans, 17-cis-                                                        prostadienoic acid                                      1100   300            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-trans,                                                       17-cis-prostadienoic                                                          acid and 9α,15-di-                                                      hydroxy-15-methyl-3-                                                          thia-13-trans, 17-cis-                                                        prostadienoic acid                                      1101   733            9-oxo-15-hydroxy-15-                                                          methyl-13-cis, 17-cis-                                                        prostadienoic acid and                                                        9α,15-dihydroxy-15-                                                     methyl-13-cis, 17-cis                                                         prostadienoic acid                                      ______________________________________                                         *methyl 15-hydroxy-9-oxo-13-cis-prostenoate only                         

EXAMPLES 1102-1104

Hydrogenation of the 13-trans-prostenoic acids listed in Table 19 belowby the procedure described in Example 699 is productive of the productprostanoic acids of the table. The product epimers are separable bychromatographic procedures.

                  TABLE 19                                                        ______________________________________                                               Starting 15-hy-                                                               droxy-15-methyl-                                                                              Product 15-hydroxy-                                    Ex-    13-trans-pros-  15-methyl-prostanoic                                   ample  tenoic acid     acid                                                   ______________________________________                                        1102   9-oxo-15-hydroxy-                                                                             9-oxo-15-hydroxy-15-                                          15-methyl-3-oxa-                                                                              methyl-3-oxa-prostanoic                                       13-trans-pros-  acid                                                          tenoic acid                                                                   (Example 1085)                                                         1103   9α,15-dihydroxy-                                                                        9α,15-dihydroxy-15-                                     15-methyl-3-oxa-                                                                              methyl-3-oxa-pros-                                            13-trans-pros-  tanoic acid                                                   tenoic acid                                                                   (Example 1085)                                                         1104   9-oxo-15-hydroxy-                                                                             9-oxo-15-hydroxy-15-                                          15-methyl-10a-  methyl-10a-homo-pros-                                         homo- 13-trans- tanoic acid                                                   prostenoic acid                                                               (Example 1089)                                                         ______________________________________                                    

EXAMPLE 1105 Preparation of allcis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxido-cyclopentanol

A solution 1.42 g. (10.0 moles) ofall-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde- -lactol (E. J. Coreyand R. Noyori, Tetrahedron Letters, 1970, 311) in 5 ml. of DMSO is addedto a stirred solution with the Whttig reagent [E. J. Corey et al, JACS,91 5675 (1969)] also Example 1108 prepared from 13.3 g. (30 moles) of4-carboxybutyltriphenylphosphonium bromide 2.52 g. (60 moles) of 57%sodium hydride dispersion, and 70 ml. of DMSO at 16°C. during 1 minute.

The solution is stirred at ambient temperature for 20 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The organic phase is separated, and the aqueous phase is extractedwith methylene chloride, saturated with sodium chloride, and extractedwith ether. The combined organic extracts are partitioned with sodiumbicarbonate. The aqueous basic extract is acidified with dilute HCl,saturated with sodium chloride, and extracted with ethyl acetate. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give the crude title compound as an orange oil.

EXAMPLE 1106 Preparation ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxido-cyclopentanone

To a stirred solution of ca. 1.6 moles of crudeall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example1105) in 1.6 ml. of ether is added 1.6 ml. of 4.0 N chromic acid in 4Nsulfuric acid at 0°C. during 9 minutes. After stirring for 5 minutes at0°C. the solution is diluted with brine, ether, and ethyl acetate. Theorganic phase is treated with isopropanol, washed with brine and driedover magnesium sulfate. Evaporation of the solvent gives the subjectcompound as an oil.

EXAMPLE 1107 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of 1.0 mmole ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example1106) and 3.0 mmoles of sodium carbonate in 15 ml. of water is allowedto stand at room temperature for 3 hours. The solution is acidified withHCl, saturated with sodium chloride, and extracted with ether. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give a mixture of the title compound and the isomericcompound, 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one.Further treatment of this mixture with N/10 sodium hydroxide at roomtemperature for 30 minutes causes the rearrangement of the latter isomerto the title compound, which is isolated from basic solution as above.

EXAMPLE 1107a Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

Treatment ofcis-anti-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (E. J.Corey and R. Noyori Tetrahedron Letters, 1970, 311) with4-carboxybutyltriphenylphosphonium bromide as described in Example 1105is productive of2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentan-1.beta.-ol which onon oxidation by the method of Example 1106 provides2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentanone, which in time ontreatment with aqueous base by the procedure of Example 1107 furnishesthe subject compound.

EXAMPLE 1108 Preparation of 4-carboxybutyltriphenylphosphonium bromide

A mixture of 103 g. of 5-bromovalevic acid and 152 g. oftriphenylphosphine in 400 ml. of acetonitrile is refluxed for 48 hours,cooled, diluted with 100 ml. of benzene and allowed to crystallize. Thecrystals are filtered, washed with benzene and ether, to yield colorlessmaterial, m.p. 207°-209°C.

EXAMPLES 1109-1111

Treatment of the indicated ω-bromoalkanoic acids of Table 20 below withtriphenylphosphine by the method described in Example 1108 produces thephosphonium bromides of the table.

                  TABLE 20                                                        ______________________________________                                        Ex-   Starting ω-bromo-                                                                        Product                                                ample alkanone acid    Phosphonium bromide                                    ______________________________________                                        1109  4-bromo-n-butyric                                                                              3-carboxypropyltri-                                          acid             phenylphosphonium                                                             bromide                                                1110  6-bromo-n-hexanoic                                                                             5-carboxypentyltri-                                          acid             phenylphosphonium                                                             bromide                                                1111  7-bromo-n-hepta- 6-carboxyhexyltri-                                           noic acid        phenylphosphonium                                                             bromide                                                ______________________________________                                    

EXAMPLES 1112-1114

Treatment of all cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactolwith the Wittig reagent prepared from the indicated phosphonium bromidesof Table 21 below, all by the procedure of Example 1105 is productive ofthe product compounds of the table.

                  TABLE 21                                                        ______________________________________                                        Ex-   Reagent phos-  Product                                                  ample phonium bromide                                                                              3,4-oxidocyclopentanol                                         of Example                                                              ______________________________________                                        1112  1109           all cis-2-(5-carboxy-2-                                                       cis-pentenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                       1113  1110           all cis-2-(7-carboxy-2-                                                       cis-heptenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                       1114  1111           all cis-2-(8-carboxy-2-                                                       cis-octenyl)-3,4-oxi-                                                         docyclopentan-1-ol                                       ______________________________________                                    

EXAMPLES 1115-1117

Oxidation of the cyclopentanols indicated in Table 22 below by themethod described in Example 1106 furnishes the corresponding product3,4-oxidocyclopentanones of the table.

                  TABLE 22                                                        ______________________________________                                        Ex-   Starting cyclo-                                                                              Product                                                  ample pentan-1-ol of 3,4-oxidocyclopent-                                            Example        an-1-one                                                 ______________________________________                                        1115  1112           11 cis-2-(5-carboxy-                                                          2-cis-pentenyl)-3,4-                                                          oxidocyclopentan-1-                                                           one                                                      1116  1113           all cis-2-(7-carboxy-                                                         2-cis-heptenyl)-3,4-                                                          oxidocyclopetan-1-                                                            one                                                      1117  1114           all cis-2-(8-carboxy-                                                         2-cis-octenyl)-3,4-                                                           oxidocyclopentan-1-                                                           one                                                      ______________________________________                                    

EXAMPLES 1118-1120

Alkaline treatment of the 3,4-oxidocyclopentanones of Table 23 below bythe process described in Example 1107 is productive of the4-hydroxycyclopentenones of the table.

                  TABLE 23                                                        ______________________________________                                        Ex-   Starting 3,4-    Product                                                ample oxidocyclo-      4-hydroxycyclo-                                              pentanone of     pent-2-en-1-one                                              Example                                                                 ______________________________________                                        1118    1115           2-(5-carboxy-2-                                                               cis-pentenyl)-4-                                                              hydroxycyclo-                                                                 pent-2-en-1-one                                        1119    1116           2-(7-carboxy-2-                                                               cis-heptenyl)-                                                                4-hydroxycyclo-                                                               pent-2-en-1-one                                        1120    1117           2-(8-carboxy-2-                                                               cis-octenyl)-4-                                                               hydroxycyclo-                                                                 pent-2-en-1-one                                        ______________________________________                                    

EXAMPLES 1121-1124

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 24 belowwith dihydropyran (in the manner of Example 95) is productive of thecorresponding bis-tetrahydropyranyl ether-ester of the table.

                  TABLE 24                                                        ______________________________________                                        Ex-   Starting 4-hy-                                                                              Product                                                   ample droxycyclopent-                                                                             bis-tetrahydropyranyl                                           2-en-1-one of ether-ester                                                     Example                                                                 ______________________________________                                        1121    1107        4-tetrahydropyranyloxy-                                                       2-(6-carbotetrahydro-                                                         pyranyloxy-2-cis-hexenyl)                                                     cyclopent-2-en-1-one                                      1122    1118        4-tetrahydropyranyloxy-                                                       2-(5-carbotetrahydro-                                                         pyranyloxy-2-cis-pent-                                                        enyl)cyclopent-2-en-1-                                                        one                                                       1123    1119        4-tetrahydropyranyloxy-                                                       2-(7-carbotetrahydro-                                                         pyranyloxy-2-cis-heptenyl)-                                                   cyclopent-2-en-1-one                                      1124    1120        4-tetrahydropyranyloxy-                                                       2-(8-carbotetrahydro-                                                         pyranyloxy-2-cis-octenyl)-                                                    cyclopent-2-en-1-one                                      ______________________________________                                    

EXAMPLES 1125-1130

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 25 belowwith the indicated trialkylsilyl chloride by the method described inExample 958 is productive of the bis-trialkylsilyl ether-esters of thetable.

                                      TABLE 25                                    __________________________________________________________________________         Starting 4-hydroxy-                                                      Example                                                                            cyclopentenone of                                                                         Trialkylsilyl-                                                                        Product                                                   Example     chloride                                                                              bis-trialkylsilyl ether-ester                        __________________________________________________________________________    1125 1107        (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(6-carbotrimethyl-                                        siloxy-2-cis-hexenyl)cyclopent-2-en-1-one            1126 1118        (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(5-carbotrimethyl-                                        siloxy-2-cis-pentenyl)cyclopent-2-en-1-one           1127 1119        (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(7-carbotrimethyl-                                        siloxy-2-cis-heptenyl)cyclopent-2-en-1-one           1128 1120        (CH.sub.3).sub.3 SiCl                                                                 4-trimethylsiloxy-2-(8-carbotrimethyl-                                        siloxy-2-cis-octenyl)cyclopent-2-en-1-one            1130 1107        dimethyliso-                                                                          4-dimethylisopropylsiloxy-2-(6-carbodi-                               propyl silyl                                                                          methylisopropylsiloxy-2-cis-hexenyl)cyclo-                            chloride                                                                              pent-2-en-1-one                                      __________________________________________________________________________

EXAMPLE 1131 Preparation of 1-oxo-2-hydroxy-bicyclo[3.3.0]oct-4-ene

A solution of 6.2 g. (50 mole) of the lactone ofcis-2-hydroxycyclopent-4-ene-1-acetic acid [P. A. Grieco, J. Org. Chem.,37, 2363 (1972)] in 350 ml. toluene (dried over molecular sieves) iscooled to -75°C. and treated dropwise under nitrogen with 84 ml. 0.89 Mdiisobutyl aluminum hydride (10.55 g., 74 mole) over a period of aboutone hour maintaining the temperature at -74 ± 2°C. The resulting clearsolution is stirred at -75°C. for 2 hours and poured with stirring intoa mixture of 15 ml. of concentrated hydrochloric acid and 300 ml. of icewater. The mixture is stirred while warming to room temperature. Thelayers are separated and the aqueous layer is treated with salt andextracted with three small portions of ether. The combined organicportions are dried over sodium sulfate and evaporated at reducedpressure (75°C. water bath) to yield the product (homogeneous by thinlayer chromatography) as a pale yellow mobile liquid.

EXAMPLE 1132 Preparation of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene

A solution of the sodium salt of dimethyl sulfoxide is prepared bystirring under nitrogen a mixture of 160 ml. dry dimethyl sulfoxide(dried over molecular sieves and a few pellets of calcium hydride) with6.0 g. (0.25 mole) of sodium hydride (prepared by washing 10.5 g. of 57%sodium hydride dispersion in mineral oil with two 30 ml. portions ofhexane.) The mixture is warmed with stirring at 75°C. (oil bath) for 2.5hours.

This solution is added over about five minutes to a solution undernitrogen of 44 grams (0.1 mole) of 4-carboxybutyltriphenylphosphoniumbromide (Example 1108) in 180 ml. of dry dimethyl sulfoxide. Theresulting dark reddish brown solution is stirred for 10 minutes, cooledto room temperature and treated with a solution of crude1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene (6.2 g., 50 mole) (Example 1131)in 20 ml. of anhydrous dimethyl sulfoxide. The resulting solution isstirred 16 hours and then treated with 250 ml. of ice water.

This brown solution is extracted with two portions of ether to removeneutral material then made strongly acidic with hydrochloric acid. Thesolution is extracted into four 100 ml. portions of methylene chloride.The combined methylene chloride extracts are washed with water, thenextracted with four 100 ml. portions of 5% sodium bicarbonate. Thecombined aqueous extracts are washed with methylene chloride and madeacidic to Congo Red with concentrated hydrochloric acid. The mixture isextracted with three 100 ml. portions of methylene chloride. The organicextracts are combined dried over sodium sulfate and the solvent isevaporated at reduced pressure. The residue (an oily solid) is extractedseveral times with ether and the ethereal extracts are combined andevaporated at reduced pressure to yield the crude product as a dark oil.The product is purified by chromatograph6 on silica gel, eluting withether. The product is a colorless liquid.

EXAMPLE 1133 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one

A solution of 3.2 g. (0.5 mole) of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene (Example 1132) in60 ml. of reagent acetone is treated dropwise with a total of 6 ml. of8N chromic acid in sulfuric acid at 0°C. The oxidation is rather slow.The resulting mixture is dissolved in 200 ml. of water and the solutionis extracted with six 50 ml. portions of ether. The combined etherealextracts are dried over sodium sulfate and the solvent is evaporated atreduced pressure to yield the product as a yellow oil.

EXAMPLE 1134 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-2-en-1-one

A solution of 3 g. of crude2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one (Example 1133) in 100ml. of 2% sodium hydroxide is stirred at 80°C. under nitrogen for 1.5hours. The cooled solution is acidified to Congo Red and extracted intoether. The ethereal extracts are dried over sodium sulfate andevaporated at reduced pressure to afford the product.

EXAMPLES 1135-1137 Treatment of 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-eneby the procedure described in Example 1132 with the ylids derived fromthe phosphonium bromides listed in Table 26 below furnishes the product1-hydroxy-cyclopent-3-enes of the table.

                  TABLE 26                                                        ______________________________________                                        Ex-   Starting phos- Product                                                  ample phonium bromide                                                                              1-hydroxy-2-(ω-carboxy-                                  of Example     2-cis-alkenyl)cyclopent-                                                      3-enes                                                   ______________________________________                                        1135    1109         1-hydroxy-2-(5-carboxy-                                                       2-cis-pentenyl)cyclo-                                                         pent-3-ene                                               1136    1110         1-hydroxy-2-(7-carboxy-                                                       2-cis-heptenyl)cyclo-                                                         pent-3-ene                                               1137    1111         1-hydroxy-2-(8-carboxy-                                                       2-cis-octenyl)cyclo-                                                          pent-3-ene                                               ______________________________________                                    

EXAMPLES 1138-1140

Oxidation of the 1-hydroxycyclopent-3-enes listed in Table 27 below bythe procedure described in Example 1133 is productive of the productcyclopent-3-en-1-ones of the table.

                  TABLE 27                                                        ______________________________________                                        Ex-   Starting 1-    Product                                                  ample hydroxycyclo-  2-(107 -carboxy-2-cis-                                         pent-3-ene of  alkenyl)cyclopent-3-                                           Example        en-1-one                                                 ______________________________________                                        1138    1135         2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-3-                                                         en-1-one                                                 1139    1136         2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-3-                                                         en-1-one                                                 1140    1137         2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-3-                                                          en-1-one                                                 ______________________________________                                    

EXAMPLES 1141-1143

Base treatment according to the procedure described in Example 1134 ofthe cyclopent-3-ene-1-ones listed in Table 28 below is productive of theproduct cyclopent-2-en-1-ones of the table.

                  TABLE 28                                                        ______________________________________                                        Ex-   Starting 2-(ω-                                                                          Product                                                 ample carboxy-2-cis-  2-(ω-carboxy-2-cis-                                     alkenyl)cyclo-  alkenyl)cyclopent-                                            pent-3-ene-1-   2-en-1-one                                                    one of Example                                                          ______________________________________                                        1141    1138          2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-                                                           2-en-1-one                                              1142    1139          2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-                                                           2-en-1-one                                              1143    1140          2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-                                                            en-en-1-one                                             ______________________________________                                    

EXAMPLES 1144-1146

Treatment of the listed 2-(ω-carboxy-2-cis-alkenyl)cyclopent-2-en-1-oneof Table 29 below with diazomethane in the usual manner is productive ofthe product methyl esters of the table.

                  TABLE 29                                                        ______________________________________                                        Ex-   Starting car- Product                                                   ample boxylic acid  2-(ω-carbomethoxy-2-cis-                                  of Example    alkenyl)cyclopent-2-en-                                                       1-one                                                     ______________________________________                                        1144    1141        2-(5-carbomethoxy-2-cis-                                                      pentenyl)cyclopent-2-en-                                                      1-one                                                     1145    1142        2-(7-carbomethoxy-2-cis-                                                      heptenyl)cyclopent-2-en-                                                      1-one                                                     1146    1143        2-(8-carbomethoxy-2-cis-                                                      octenyl)cyclopent-2-en-                                                       1-one                                                     ______________________________________                                    

EXAMPLES 1147-1149

Treatment by the procedure of Example 120 of the cyclopentenones listedin Table 30 below with lithiumdiisobutylmethyl-(3-triphenylmethoxy-1-trans-5-cis-octadienyl) alanate,also prepared by the procedure of Example 120 from3-triphenylmethoxy-cis-5-en-octyne-1 (Example 139), diisobutylaluminumhydride and methyl lithium, followed by hydrolysis of the intermediate15-triphenylmethoxy derivatives by treatment with aceticacid-tetrahydrofuran-water (4:2:1) in the manner of Example 121, andthen by saponification of the intermediate methyl esters by the processdescribed in Example 122 is productive of the product prostatrienoicacids of the table.

                  TABLE 30                                                        ______________________________________                                        Ex-   Starting 2-(ω-                                                                         Product                                                  ample carbomethoxy-2-                                                                              9-oxo-15-hydroxy-5-                                            cis-alkenyl)-  cis, 13-trans,17-cis-                                          cyclopent-2-en-                                                                              prostatrienoic acids                                           1-one of Example                                                        ______________________________________                                        1147    1144         9-oxo-4-nor-15-hydroxy-                                                       5-cis-13-trans-17-                                                            cis-prostatrienoic                                                            acid                                                     1148    1145         9-oxo-4a-homo-15-hydro-                                                       xy-5-cis-13-trans-17-                                                         cis-prostatrienoic                                                            acid                                                     1149    1146         9-oxo-4a-bishomo-15-hy-                                                       droxy-5-cis-13-trans-                                                         17-cis-prostatrienoic                                                         acid                                                     ______________________________________                                    

EXAMPLES 1150-1159

Treatment of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listedin Table 31 below with lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl] according to theprocedure described in Example 960 is productive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadienoic acids of the tableas well as of the corresponding 15-epi derivatives, separable from thelisted 15-normal derivatives by chromatography.

                  TABLE 31                                                        ______________________________________                                        Ex-   Starting blocked                                                        ample 4-oxycyclopent-                                                                              9-oxo-11α,15-dihydroxy-                                  2-en-1-one of  5-cis,13-trans-pros-                                           Example        tadienoic acids                                          ______________________________________                                        1150    1121         9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1151    1125         9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1152    1130         9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                         1153    1122         9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                       1154    1126         9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                       1155    1123         9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                       1156    1127         9-oxo-11a,15-dihydroxy-                                                       4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                       1158    1124         9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                     1159    1128         9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                     ______________________________________                                    

EXAMPLES 1160-1169

Treatment by the procedure described in Example 123 of the ether-esterblocked 4-oxycyclopent-2-en-1-ones listed in Table 32 below with lithiumdiisobutylmethyl(3-triphenylmethoxy-1-trans-5-cis-octadienyl)alanate,prepared from 3-triphenylmethoxy-cis-5-en-octyne-1- (Example 139) by theprocedure of Example 120, followed by the cleavage of blocking groupsand isolation of products by the method described in Example 124 isproductive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-prostatrienoic acids of thetable; also formed are the corresponding 15-epi derivatives which areseparable by chromatography from the listed 15-normal derivatives.

                  TABLE 32                                                        ______________________________________                                               Starting blocked                                                                            Product                                                  Ex-    4-oxycyclopent-                                                                             9-oxo-11α,15-dihydroxy-                            ample  2-en-1-one of 5-cis,13-trans,17-cis-                                          Example       prostatrienoic acids                                     ______________________________________                                        1160   1121          9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-                                                            cis-prostatrienoic                                                            acid (prostaglandin E.sub.3)                             1161   1125          9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                                  1162   1130          9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans 17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                                  1163   1122          9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                     1164   1126          9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                     1165   1123          9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                            1166   1127          9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                            1168   1124          9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis,                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                            1169   1128          9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis-                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                            ______________________________________                                    

EXAMPLE 1170 Preparation of 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoic acid

Treatment in the manner described in Example 733 of4-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxy-2-cis-hexenyl)cyclopent-2-en-1-one(Example 1121) with the Grignard reagent prepared from magnesium and1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) also asdescribed in Example 733 in the presence of cuprous iodidetri-n-butylphosphine complex is productive after chromatography ofprostaglandin E₂ and 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoicacid.

EXAMPLES 1171 and 1172

Treatment of the two 9-oxo derivative listed in Table 33 below withlithium perhydro-9b-boraphenalylhydride in the manner described inExample 737 furnishes the indicated 9α,15-dihydroxy-13-cis-prostenoicacids.

                  TABLE 33                                                        ______________________________________                                        Ex-    Starting 9-oxo-                                                                             Product                                                  ample  derivative of 9α,15-dihydroxy-13-cis-                                   Example       prostenoic acids                                         ______________________________________                                        1171   736           9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                          1172   1170          9α,15-dihydroxy-5-cis-                                                  prostadienoic acid                                       ______________________________________                                    

EXAMPLE 1173 Preparation of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

To an ice cooled solution of 3.5 g. (50 moles) of 2-methyl-2-butene in25 ml. of tetrahydrofuran under an inert atmosphere is added 25 ml. of 1M diborane in tetrahydrofuran dropwise over 10 minutes. The mixture isstirred at 0-5°C. for 2 hours and then the solvent is removed undervacuum. The residue is dissolved in 20 ml. of carbon tetrachloride andto the resulting solution cooled to 0°C. is added a solution of 5.25 g.(22 mole) of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995)in 10 ml. of carbon tetrachloride over 10 minutes. The cooling bath isremoved and the mixture is allowed to stir at ambient temperature for1.5 hours. The mixture is cooled to 0°C. and a solution of 3.52 g. (22moles) of bromine in 15 ml. of carbon tetrachloride is added over 10minutes. The cooling bath is removed and the mixture is refluxed for 6hours under an inert atmosphere. The mixture is cooled and poured intodilute sodium hydroxide solution. The organic phase is washed with waterand saturated brine, dried (Na₂ SO₄), and evaporated. The residue ischromatographed upon silica gel and the title compound is isolated with5% ethyl acetate in benzene.

EXAMPLE 1174 Preparation of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol

A mixture of 3.19 g. (10 moles) of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example1173) and 90 ml. of 3:1:1 tetrahydrofuran-acetic acid-water is stirredat ambient temperatures for 20 hours. The solvent is evaporated in vacuoand the residue is chromatographed on silica gel. The title compound isisolated using 10-20% ethyl acetate in benzene.

EXAMPLE 1175 Preparation of1-bromo-4,4-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 1.88 g. (8 moles) of1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8moles) of triphenylmethyl bromide in 20 ml. of pyridine and purificationof Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1176 Preparation of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

Treatment of 7.15 g. (30 moles) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) with 33 molesof disiamylborane in carbon tetrachloride followed by 30 moles ofbromide in carbon tetrachloride, refluxing the resulting mixture, andisolation by chromatography on silica gel, all as described in Example1173 gives the title compound.

EXAMPLE 1177 Preparation of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol

Treatment of 7.35 g. (23 moles) of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example1176) with 200 ml. of 3:1:1 tetrahydrofuran-acetic acid-water andpurification on silica gel all as described in Example 1174 gives thetitle compound.

EXAMPLE 1178 Preparation of1-bromo-5,5-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 3.53 g. (15 moles) of1-bromo-5,5-dimethyl-trans-1-octen-3-ol (Example 1177) with 4.85 g. (15moles) of triphenylmethyl bromide in 35 ml. of pyridine and purificationon Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1179 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

To a mixture of 0.650 g. (16.91 mole) of sodium borohydride and 3.17 g.(45.2 moles) of 2-methyl-2-butene in 40 ml. of diglyme cooled to -5°C.under an inert atmospere is added over 15 minutes 3.24 g. (22.6 moles)of boron trifluoride ethereate and the resulting mixture is stirred at0°C. for 2 hours. To this mixture is then added over 5 minutes 8.32 g.(22.6 moles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. ofdiglyme, the cooling bath is removed, and the mixture is stirred atambient temperatures for 1.5 hours. The mixture is cooled to 0°C. and6.0 g. of finely divided anhydrous trimethylamine oxide is added over 10minutes. The cooling bath is removed and the mixture is stirred atambient temperatures for 0.5 hour. The mixture is then poured into 200ml. of 15% sodium hydroxide solution, a solution of 16 g. (63 moles) ofiodine in 20 ml. of tetrahydrofuran is added immediately, and theresulting mixture is stirred for 0.5 hour. The organic phase isseparated and the aqueous phase is washed with ether. The combinedorganic phase and washings are decolorized with 5% sodium thiosulfatesolution, washed with saturated brine, dried (Na₂ SO₄), and evaporated.The residue is dry-columned chromatographed upon alumina using hexane aseluent and the title compound is isolated as an oil.

EXAMPLE 1180 Preparation of 3-triphenylmethoxy-cis-oct-5-en-1-yne

Treatment of 22 g. of cis-oct-5-en-1-yne-3-ol, prepared according to theprocedure of J. Fried, C. H. Lin, J. C. Sih, P. Dalven, G. F. Cooper, J.Amer. Chem. Soc., 94, 4342 (1972), with 58 g. of triphenylmethyl bromidein 100 ml. of pyridine and purification on Florisil, all as described inExample 728 gives the title compound.

EXAMPLE 1181 Preparation of1-iodo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 20 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne with 55moles of disiamylborane in diglyme, followed by trimethylamine oxide,aqueous sodium hydroxide, and iodine, and purification of alumina, allas described in Example 1179, gives the title compound.

EXAMPLE 1182 Preparation of1-bromo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 15 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne (Example1180) with 41 moles of disiamylborane in tetrahydrofuran, replacing thesolvent with carbontetrachloride, addition of 41 moles of bromine, andrefluxing the mixture, all as described in Example 1173, andpurification of the material upon Florisil as described in Example 728gives the title compound.

EXAMPLE 1183 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisamylborane, trimethylamine oxide and iodine by the proceduredescribed in Example 1179 is productive of the subject compound.

EXAMPLE 1184 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane, trimethylamine oxide and iodine by the process describedin Example 1179 is productive of the subject compound.

EXAMPLE 1185 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisiamylborane and the bromide by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1186 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane and the bromine by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1187 Preparation of the Grignard reagent of1-bromo-3-triphenylmethoxy-trans-1-octene at 33°C.

To a slurry of 0.585 g. (0.0241 g. atom) of magnesium and 5 ml. oftetrahydrofuran under an argon atmosphere is added 2 ml. of a solutionof 7.536 (0.0168 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728) in 10 ml. of tetrahydrofuran. The mixture is warmed to35°C. and reaction is initiated with 1 drop of methyl iodide. Thereaction is allowed to exotherm to 37°C. and then to cool to 33°C.whereupon the remainder of the halide is added at a rate to maintain33°C. After complete addition of the halide, the mixture is stirred at33°C. for 1 hour and is separated from the excess magnesium to yield atetrahydrofuran solution of the title Grignard reagent.

EXAMPLE 1188 Preparation of 11-deoxy-8β-methyl-prostaglandin E₁ methylester, 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester, methyl15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate, and methyl15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate

The Grignard reagent, prepared as described in Example 1187 from 0.585g. of magnesium, 7.536 g. of 1-bromo-3-triphenylmethoxy-trans-1octene(Example 728), and 10 ml. of tetrahydrofuran, is added to an ice cooledsolution of 3.76 of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example83) and 0.305 g. of copper (I) iodide-tri-n-butylphosphine complex in 10ml. of tetrahydrofuran over 10 minutes under an inert atmosphere. Themixture is stirred with cooling for 0.5 hour and to it is then added 46g. of methyl iodide. The cooling bath is removed and the mixture isstirred at ambient temperatures for 48 hours. The mixture is poured intosaturated ammonium chloride solution and is extracted into ether. Theorganic phase is washed with saturated brine and is evaporated. Theresidue is heated to 80°C. with 100 ml. of 80% aqueous acetic acid for0.5 hour and the mixture is then evaporated to dryness. The residue isdry-column chromatography upon silica gel using 4:1 benzene-ethylacetate as eluent to afford a mixture of11-deoxy-8β-methyl-prostaglandin E₁ methyl ester and 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester and a mixture of methyl15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate and methyl15-hydroxy-8α-methyl-9 oxo-8-iso-13-cis-prostenoate. Further separationof the 8β and 8α isomers is accomplished by a combination of partitionchromatography and thin layer chromatography.

EXAMPLES 1190-1205

Treatment by the procedure of Example 1188 of the cyclopentenones listedin Table 34 below with the Grignard reagent; prepared as described inExample 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyl iodide furnishesthe product 8α and 8β0 methyl prostenoates of the table. The productsare all obtained via the corresponding 15-O-triphenylmethyl derivatives,which are hydrolytically cleaved as described in Example 1188.

                                      Table 34                                    __________________________________________________________________________    Example                                                                            Starting cycloalkenene                                                                    Starting 1-bromo-3-                                                                       Product 8-alkyl prostenoates                          of Example  triphenylmethoxy-1-                                                           trans-alkene of                                                               Example                                                      __________________________________________________________________________    1190 13          1175        ethyl 8-β-methyl-9-oxo-15-hydroxy-16,16-                                 N                                                                             dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 O                                                                             dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-                                  y                                                                             dimethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 0                                                                             dimethyl-8-iso-13-cis-prostenoate                1191 13          1178        ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  5                                                                             dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 J                                                                             dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  u                                                                             dimethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 n                                                                             dimethyl-8-iso-13-cis-prostenoate                1192 13          1182        ethyl 8β -methyl-9-oxo-15-hydroxy-13-tra                                 ns,                                                                           17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 13-                                                                           trans,17-cis-prostadienoate                                                   ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,                                 J                                                                             17-cis-prostadienoate                                                         ethyl 8α-9-oxo-15-hydroxy-8-iso-                                        13-cis, 17-cis-prostadienoate                    1193 13          1185        ethyl 8β -methyl-9-oxo-15-hydroxy-20-eth                                 yl-                                                                           13-trans-postenoate                                                           ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                 yl-                                                                           8-iso-13-trans-prostenoate                                                    ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                 l-                                                                            13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 20-                                                                           ethyl-13-cis-prostenoate                         1194 84          1186        decyl 8β -methyl-9-oxo-15-hydroxy-20-                                    methyl-13-trans-prostenoate                                                   decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-trans-prostenoate                                             decyl 8β-methyl-9-oxo-15-hydroxy-20-                                     methyl-13-cis-prostenoate                                                     decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-cis-prostenoate                  1195 23          728         ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  A                                                                             bishomo-13-trans-prostenoate                                                  ethyl 8α-9-oxo-15-hydroxy-7a,7b-                                        bishomo-8-iso-13-trans-prostenoate                                            ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  u                                                                             bishomo-13-cis-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                 g                                                                             bishomo-8-iso-13-cis-prostenoate                 1196 31          1185        ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  0                                                                             bisethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  8                                                                             bisethyl-8-iso-13-cis-prostenoate                1197 46          1175        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                 6,                                                                            16-dimethyl-13-trans-prostenoate                                              ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 16,                                                                           16-dimethyl-8-iso-13-trans-prostenoate                                        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                 6,                                                                            16-dimethyl-13-cis-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 16,                                                                           16-dimethyl-8-iso-13-cis-prostenoate             1198 46          1182        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  p                                                                             13-trans,17-cis-prostadienoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 0                                                                             8-iso-13-trans,17-cis-prostadienoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  9                                                                             13-cis,17-cis-prostadienoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 O                                                                             8-iso-13-cis,17-cis-prostadienoate               1199 53          1186        ethyl 8β-methyl-9-oxo-15                                                 -hydroxy-7-nor-                                                               20-methyl-13-trans-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 c                                                                             20-methyl-8-iso-13-trans-prostenoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-                                  t                                                                             20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 1                                                                             20-methyl-8-iso-13-cis-prostenoate               1200 70          1178        ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluor                                 o-                                                                            17,17-dimethyl-13-trans-prostenoate                                           ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluo                                 ro-                                                                           17,17-dimethyl-8-iso-13-trans-prostenoate                                     ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluor                                 o-                                                                            17,17-dimethyl-13-cis-prostenoate                                             ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluo                                 ro-                                                                           17,17-dimethyl-8-iso-13-cis-prostenoate          1201 111         728         ethyl 8β-methyl-9-oxo-15-hydroxy-10a-hom                                 o-                                                                            13-trans-prostenoate                                                          ethyl 8α-methyl-9-oxo-15-hydroxy-10a-ho                                 mo-                                                                           8-iso-13-trans-prostenoate                                                    ethyl 8β-methyl-9-oxo-15-hydroxy-10a-hom                                 o-                                                                            13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-10a-ho                                 mo-                                                                           8-iso-13-cis-prostenoate                         1202 79          1186        ethyl 8β-methyl-9-oxo-15-hydroxy-2-pheny                                 l-                                                                            20-methyl-13-trans-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-2-phen                                 yl-                                                                           20-methyl-8-iso-13-trans-prostenoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-2-pheny                                 l-                                                                            20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phen                                 yl-                                                                           20-methyl-8-iso-13-cis-prostenoate               1203 900         1182        methyl 8β-methyl-9-oxo-15-hydroxy-                                       5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8α-methyl-9-oxo-15-hydroxy-8-iso                                 -                                                                             5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                 13-cis,17-cis-prostatrienoate                                                 methyl 8α-methyl-9-oxo-15-hydroxy-8-iso                                 -                                                                             5-cis,13-cis,17-cis-prostatrienoate              1204 900         728         ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-trans-prostadienoate                                                       ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 5-cis,13-trans-prostadienoate                                                 ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 1                                                                             5-cis,13-cis-prostadienoate                      1205 900         1185        ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                 l-                                                                            5-cis,13-trans-prostadienoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                 yl-                                                                           8-iso-5-cis,13-trans-prostadienoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                 l-                                                                            5-cis,13-cis-prostadienoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                 yl-                                                                           8-iso-5-cis,13-cis-prostadienoate                __________________________________________________________________________

EXAMPLES 1206-1273

Treatment of the designated 9-oxo-prostenoic acid and ester derivativesin Table 35 below with sodium borohydride in ethanol as described inExample 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are seperable by standard chromatographic techniques.

                  TABLE 35                                                        ______________________________________                                        Ex-    Starting 9-oxo-                                                                              Product 9-hydroxy                                       ample  derivative     derivatives                                             ______________________________________                                        1206   11-deoxy-8β-                                                                            11-deoxy-8β-methyl-pros-                                  methyl-prosta- taglandin F.sub.1 α and F.sub.1 β                   glandin E.sub.1 meth-                                                                        methyl esters                                                  yl ester                                                                      (Example 1188)                                                         1207   11-deoxy-8α-                                                                           11-deoxy-8α-methyl-8-iso-                                methyl-8-iso-  prostaglandin F.sub.1 α and                              prostaglandin  F.sub.1 β methyl esters                                   E.sub.1 methyl ester                                                          (Example 1188)                                                         1208   methyl 15-hy-  methyl 9α/β, 15-di                                  droxy-8β-meth-                                                                          hydroxy-8β-methyl-13-                                     yl-9-oxo-13-   cis-prostenoates                                               cis-prostenoate                                                               (Example 1188)                                                         1209   methyl 15-hy-  methyl 9α/β, 15-dihydroxy                           droxy-8α-meth-                                                                         8α-methyl-8-iso-13-cis-                                  yl-9-oxo-13-   prostenoates                                                   cis-prosteno-                                                                 ate (Example                                                                  1188)                                                                  1210   ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16-    yl-13-trans-prosteno-                                          16-dimethyl-   ates                                                           13-trans-                                                                     prostenoate                                                                   (Example 1190)                                                         1211   ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16,-   yl-8-iso-13-trans-pros-                                        16-dimethyl-   tenoates                                                       8-iso-13-                                                                     trans-prosten-                                                                oate (Example                                                                 1190)                                                                  1212   ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-16,16-dimeth-                                        droxy-16,16-   yl-13-cis-prostenoates                                         dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1190)                                                                  1213   ethyl 8α -meth-                                                                        ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-16,16-dimeth-                                        hydroxy-16,-   yl-8-iso-13-cis-prosten-                                       16-dimethyl-8- oates                                                          iso-13-cis-                                                                   prostenoate                                                                   (Example 1190)                                                                ethyl-                                                                 1214   8β-methyl-9-                                                                            ethyl 8β-methyl-9α/β,15-                       oxo-15-hydrox- dihydroxy-17,17-dimeth-                                        y-17,17-dimeth-                                                                              yl-13-trans-prostenoates                                       yl-13-trans-                                                                  prostenoate                                                                   (Example 1191)                                                         1215   ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-   dihydroxy-17,17-dimeth-                                        hydroxy-17,17- yl-8-iso-13-trans-pros-                                        dimethyl-8-    tenoates                                                       iso-13-trans-                                                                 prostenoate                                                                   (Example 1191)                                                         1216   ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-   dihydroxy-17,17-dimeth-                                        hydroxy-17,17- yl-13-cis-prostenoates                                         dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1191)                                                                  1217   ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-hy-                                                                              dihydroxy-17,17-dimeth-                                        droxy-17,17-di-                                                                              yl-8-iso-13-cis-prosten-                                       methyl-8-iso-  oates                                                          13-cis-prosten-                                                               oate (Example                                                                 1191)                                                                  1218   ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-13-trans,17-                                         droxy-13-trans-                                                                              cis-prostadienoates                                            17-cis-prosta-                                                                dienoate (Exam-                                                               ple 1192)                                                              1219   ethyl 8α-meth-                                                                         ethyl 8α-methyl-9α/β,15-                      yl-9-oxo-15-hy-                                                                              dihydroxy-8-iso-13-trans,                                      droxy-8-iso-13-                                                                              17-cis-prostadienoates                                         trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                         1220   ethyl 8β-meth-                                                                          ethyl 8β-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                              dihydroxy-13-cis,17-                                           droxy-13-cis,- cis-prostadienoates                                            17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                  1221   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-8-iso-13-cis-                                        droxy-8-iso-13-                                                                              17-cis-prostadienoates                                         cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1192)                                                              1222   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-ethyl-13-                                         droxy-20-ethyl-13-                                                                           trans-prostenoates                                             trans-prosteno-                                                               ate (Example 1193)                                                     1223   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-ethyl-8-                                          droxy-20-ethyl-8-                                                                            iso-13-trans-prosteno-                                         iso-13-trans-  ates                                                           prostenoate                                                                   (Example 1193)                                                         1224   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-ethyl-13-                                         droxy-20-ethyl-13-                                                                           cis-prostenoates                                               cis-prostenoate                                                               (Example 1193)                                                         1225   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-ethyl-8-                                          droxy-20-ethyl-                                                                              iso-13-cis-prostenoates                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                         1226   decyl 8β-methyl-                                                                        decyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-methyl-13-                                        droxy-20-methyl-                                                                             trans-prostenoates                                             13-trans-pros-                                                                tenoate (Example                                                              1194)                                                                  1127   decyl 8α-methyl-                                                                       decyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-methyl-8-                                         droxy-20-methyl-                                                                             iso-13-trans-prosteno-                                         8-iso-13-trans-                                                                              ates                                                           prostenoate                                                                   (Example 1194)                                                         1128   decyl 8β-methyl-                                                                        decyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-20-methyl-13-                                        droxy-20-methyl-                                                                             cis-prostenoates                                               13-cis-prosten-                                                               oate (Example                                                                 1194)                                                                  1229   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-20-methyl-8-                                         droxy-20-methyl-                                                                             iso-13-cis-prostenoates                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1194)                                                         1230   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-13-trans-prosteno-                                        homo-13-trans- ates                                                           prostenoate                                                                   (Example 1195)                                                         1231   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-8-iso-13-trans-                                           homo-8-iso-13- prostenoates                                                   trans-prosteno-                                                               ate (Example                                                                  1195)                                                                  1232   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-13-cis-prosteno-                                          homo-13-cis-pros-                                                                            ates                                                           tenoate (Example                                                              1195)                                                                  1233   ethyl 8α-methyl                                                                        ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7a,7b-bis-                                           droxy-7a,7b-bis-                                                                             homo-8-iso-13-cis-pros-                                        homo-8-iso-13- tenoates                                                       cis-prostenoate                                                               (Example 1195)                                                         1234   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-13-trans-prosteno-                                       ethyl-13-trans-                                                                              ates                                                           prostenoate                                                                   (Example 1196)                                                         1235   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-8-iso-13-trans-                                          ethyl-8-iso-13-                                                                              prostenoates                                                   trans-prosteno-                                                               ate (Example                                                                  1196)                                                                  1236   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-13-cis-prosteno-                                         ethyl-13-cis-  ates                                                           prostenoate                                                                   (Example 1196)                                                         1237   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2,20-bis-                                            droxy-2,20-bis-                                                                              ethyl-8-iso-13-cis-pros-                                       ethyl-8-iso-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1196)                                                         1238   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-13-trans-pros-                                        16-dimethyl-13-                                                                              tenoates                                                       trans-prosteno-                                                               ate (Example                                                                  1197)                                                                  1239   ethyl 8α-methyl-                                                                       ethyl 8α -methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-8-iso-13-trans-                                       16-dimethyl-8- prostenoates                                                   iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                         1240   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-13-cis-pros-                                          16-dimethyl-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1197)                                                         1241   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-16,16-                                         droxy-3-oxa-16,-                                                                             dimethyl-8-iso-13-cis-                                         16-dimethyl-8- prostenoates                                                   iso-13-cis-                                                                   prostenoate                                                                   (Example 1197)                                                         1242   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-13-                                            droxy-3-oxa-13-                                                                              trans,17-cis-prostadi-                                         trans,17-cis-  enoates                                                        prostadienoate                                                                (Example 1198)                                                         1243   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-8-iso-                                         droxy-3-oxa-8- 13-trans,17-cis-prosta-                                        iso-13-trans,- dienoates                                                      17-cis-prostadi-                                                              enoate (Example                                                               1198)                                                                  1244   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-3-oxa-13-cis-                                        droxy-3-oxa-13-                                                                              17-cis-prostadienoates                                         cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                              1245   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-3-oxa-8-iso-                                         droxy-3-oxa-8-iso-                                                                           13-cis,17-cis-prosta-                                          13-cis,17-cis- dienoates                                                      prostadienoate                                                                (Example 1198)                                                         1246   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-13-trans-pros-                                          methyl-13-trans-                                                                             tenoates                                                       prostenoate                                                                   (Example 1199)                                                         1247   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-8-iso-13-trans-                                         methyl-8-iso-13-                                                                             prostenoates                                                   trans-prosteno-                                                               ate (Example 1199)                                                     1248   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-13-cis-prosteno-                                        methyl-13-cis- ates                                                           prostenoate                                                                   (Example 1199)                                                         1249   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-7-nor-20-                                            droxy-7-nor-20-                                                                              methyl-8-iso-13-cis-                                           methyl-8-iso-  prostenoates                                                   13-cis-prosteno-                                                              ate (Example                                                                  1199)                                                                  1250   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-13-trans-                                          17,17-dimethyl-                                                                              prostenoates                                                   13-trans-prosten-                                                             oate (Example                                                                 1200)                                                                  1251   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-8-iso-13-                                          17,17-dimethyl-                                                                              trans-prostenoates                                             8-iso-13-trans                                                                prostenoate                                                                   (Example 1200)                                                         1252   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-17,-                                                                          17-dimethyl-13-cis-pros-                                       17-dimethyl-13-                                                                              tenoates                                                       cis-prostenoate                                                               (Example 1200)                                                         1253   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-fluoro-17,-                                        droxy-2-fluoro-                                                                              17-dimethyl-8-iso-13-                                          17,17-dimethyl-                                                                              cis-prostenoates                                               8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                         1254   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-10a-homo-13-                                         droxy-10a-homo-13-                                                                           trans-prostenoates                                             trans-prosteno-                                                               ate (Example                                                                  1201)                                                                  1255   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-10a-homo-8-                                          droxy-10a-homo-8-                                                                            iso-13-trans-prosteno-                                         iso-13-trans-  ates                                                           prostenoate                                                                   (Example 1201)                                                         1256   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-10a-homo-13-                                         droxy-10a-homo-                                                                              cis-prostenoates                                               13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                  1257   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-10a-homo-8-                                          droxy-10a-homo-8-                                                                            iso-13-cis-prostenoates                                        iso-13-cis-pros-                                                              tenoate (Example                                                              1201)                                                                  1258   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-13-trans-prosten-                                       20-methyl-13-  oates                                                          trans-prosteno-                                                               ate (Example                                                                  1202)                                                                  1259   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-8-iso-13-trans-                                         20-methyl-8-iso-                                                                             prostenoates                                                   13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                  1260   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-13-cis-prosteno-                                        20-methyl-13-cis-                                                                            ates                                                           prostenoate                                                                   (Example 1202)                                                         1261   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-2-phenyl-20-                                         droxy-2-phenyl-                                                                              methyl-8-iso-13-cis-                                           20-methyl-8-iso-                                                                             prostenoates                                                   13-cis-prosteno-                                                              ates (Example                                                                 1202)                                                                  1262   methyl 8β-methyl-                                                                       methyl 8β-methyl-9α/β,15-                      9-oxo-15-hy-   dihydroxy-5-cis,13-                                            droxy-5-cis,13-                                                                              trans,17-cis-prostatri-                                        trans,17-cis-pros-                                                                           enoates                                                        tatrienoate                                                                   (Example 1203)                                                         1263   methyl 8α-methyl-                                                                      methyl 8α-methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-8-iso-5-cis,-                                        droxy-8-iso-5- 13-trans,17-cis-prosta-                                        cis,13-trans,17-                                                                             trienoates                                                     cis-prostatri-                                                                enoate                                                                        (Example 1203)                                                         1264   methyl 8β-methyl-                                                                       methyl 8β-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              cis,17-cis-prostatri-                                          cis,17-cis-pros-                                                                             enoates                                                        tatrienoate                                                                   (Example 1203)                                                         1265   methyl 8α-methyl-                                                                      methyl 8α-methyl-9α/β,15-                     9-oxo-15-hy-   dihydroxy-8-iso-5-cis,-                                        droxy-8-iso-5- 13-cis,17-cis-prostatri-                                       cis,13-cis,17- enoates                                                        cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                  1266   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              trans-prostadienoates                                          trans-prostadi-                                                               enoate (Example                                                               1204)                                                                  1267   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-8-iso-5-                                          droxy-8-iso-5- cis,13-trans-prosta-                                           cis,13-trans-  dienoates                                                      prostadienoate                                                                (Example 1204)                                                         1268   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-5-cis,13-                                         droxy-5-cis,13-                                                                              cis-prostadienoates                                            cis-prostadien-                                                               oate (Example                                                                 1204)                                                                  1269   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-8-iso-5-                                          droxy-8-iso-5- cis,13-cis-prostadien-                                         cis,13-cis-    oates                                                          prostadienoate                                                                (Example 1204)                                                         1270   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              5-cis,13-trans-prosta-                                         5-cis,13-trans-                                                                              dienoates                                                      prostadienoate                                                                (Example 1205)                                                         1271   ethyl 8α-methyl-                                                                       ethyl 8α -methyl-9α/β,-                       9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-8-                                                                            8-iso-5-cis,13-trans-                                          iso-5-cis,13-  prostadienoates                                                trans-prostadien-                                                             oate (Example                                                                 1205)                                                                  1272   ethyl 8β-methyl-                                                                        ethyl 8β-methyl-9α/β,-                         9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              5-cis,13-cis-prostadi-                                         5-cis,13-cis-  enoates                                                        prostadienoate                                                                (Example 1205)                                                         1273   ethyl 8α-methyl-                                                                       ethyl 8α-methyl-9α/β,-                        9-oxo-15-hy-   15-dihydroxy-20-ethyl-                                         droxy-20-ethyl-                                                                              8-iso-5-cis,13-cis-                                            8-iso-5-cis,13-                                                                              prostadienoates                                                cis-prostadien-                                                               oate (Example                                                                 1205)                                                                  ______________________________________                                    

EXAMPLES 1274-1299

In the manner of Example 93, the various cyclopentenones of Table 36,which follows, are converted to the corresponding 4-bromo derivatives.

                  TABLE 36                                                        ______________________________________                                               Starting                                                               Ex-    Cyclopentenone                                                                             Product 4-Bromocyclo-                                     ample  of Example   pentenones                                                ______________________________________                                        1274   13           4-bromo-2-(6-carbeth-                                                         oxyhexyl)-cyclopent-2-                                                        en-1-one                                                  1275   83           4-bromo-2-(6-carbo-                                                           methoxyhexyl)cyclopent-                                                       2-en-1-one                                                1276   15           4-bromo-2-(4-carbeth-                                                         oxybutyl)cyclopent-2-en-                                                      1-one                                                     1277   14           4-bromo-2-(3-carbethoxy-                                                      propyl)cyclopent-2-en-1-                                                      one                                                       1278    2           4-bromo-2-(4-carboxy-                                                         butyl)cyclopent-2-en-                                                         1-one                                                     1279    5           4-bromo-2-(3-carboxy-                                                         propyl)cyclopent-2-en-1-                                                      one                                                       1280   22           4-bromo-2-(8-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                       1281   23           4-bromo-2-(8-carbethoxy-                                                      octyl)cyclopent-2-en-1-                                                       one                                                       1282   30           4-bromo-2-(6-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                       1283   31           4-bromo-2-(6-carbethoxy-                                                      octyl)cyclopent-2-en-1-                                                       one                                                       1284   92           4-bromo-2-(6-carboxy-                                                         5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                           1285   41           4-bromo-2-(6-carbethoxy-                                                      5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                           1286   45           4-bromo-2-(6-carboxy-5-                                                       oxahexyl)cyclopent-2-                                                         en-1-one                                                  1287   46           4-bromo-2-(6-carbethoxy-                                                      5-oxahexyl)cyclopent-2-                                                       en-1-one                                                  1288   69           4-bromo-2-(6-carboxy-6-                                                       fluorohexyl)cyclopent-                                                        2-en-1-one                                                1289   70           4-bromo-2-(6-carbethoxy-                                                      6-fluorohexyl)cyclopent-                                                      2-en-1-one                                                1290   52           4-bromo-2-(5-carboxy-                                                         pentyl)cyclopent-2-en-1-                                                      one                                                       1291   53           4-bromo-2-(5-carbethoxy-                                                      pentyl)cyclopent-2-en-                                                        1-one                                                     1292   73           4-bromo-2-(7-carboxy-                                                         heptyl)cyclopent-2-en-1-                                                      one                                                       1293   74           4-bromo-2-(7-carbethoxy-                                                      heptyl)cyclopent-2-en-1-                                                      one                                                       1294   78           4-bromo-2-(6-carboxy-6-                                                       phenylhexyl)cyclopent-2-                                                      en-1-one                                                  1295   79           4-bromo-2-(6-carbethoxy-                                                      6-phenylhexyl)cyclopent-                                                      2-en-1-one                                                1296   81           4-bromo-2-(6-carbo-n-                                                         butoxyhexyl)cyclopent-                                                        2-en-1-one                                                1297   82           4-bromo-2-(6-carbo-iso-                                                       propoxyhexyl)-cyclo-                                                          pent-2-en-1-one                                           1298   84           4-bromo-2-(6-carbo-n-                                                         decyloxyhexyl)cyclopent-                                                      2-en-1-one                                                1299   98           4-bromo-2-(6-carboxy-                                                         heptyl)-cyclopent-2-en-                                                       1-one                                                     ______________________________________                                    

EXAMPLE 1300 Preparation of4-hydroxy-2-(8-carboxyoctyl)cyclopent-2-en-1-ene

To a stirred solution of 57.2 g. of crude4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 1280 ) in 500ml. of acetone and 325 ml. of water at 3°C. is added 44.1 g.(0.226moles) of silver fluoborate during a 15 minute period. The mixture isstirred at 0-3°C. for 2 hours and filtered. The filtrate is diluted withwater, saturated with solid sodium chloride, and extracted with ether.The extract is washed with saturated sodium chloride solution, driedover magnesium sulfate, and concentrated. Partition chromatography ofthe residue on Celite gives white crystals, m.p. 58°-66°C., λmax.^(MeOH)= 223 mμ (7800); νmax (KBr) = 3340 (hydroxyl groups), 1705 (carbonylgroups), and 1625 cm⁻ ¹ (olefin group).

EXAMPLE 1301 Preparation of4-acetoxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

A mixture of 51.6 g. (0.137 moles) of crude4-bromo-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g.(0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid isstirred at reflux for 4.5 hours. The mixture is cooled, and solids areremoved by filtration. The filtrate is concentrated and extracted withhot hexane. The extract is washed with saturated sodium bicarbonatesolution and saturated sodium chloride solution, dried over mangesiumsulfate, and concentrated to give an oil. The crude product is distilledat reduced pressure to give a liquid, b.p. 152°-163°C. (0.01 mm);λmax.^(MeOH) = 223 mμ (10700); νmax. = 1745 (ester carbonyl groups),1725 (ketone carbonyl groups), and 1235 cm⁻ ¹ (acetoxy group).

EXAMPLES 1302-1326

By the procedure of Example 94 the various 4-bromocyclopentenones of thefollowing Table 37 are solvolyzed in acetone-water in the presence ofsilver fluoborate to provide the product 4-hydroxycyclopentenones of theTable.

                  Table 37                                                        ______________________________________                                               Starting 4-bromo                                                                             Product                                                 Ex-    cyclopentenones                                                                              4-Hydroxycyclopent-2-                                   ample  of Example     en-1-ones                                               ______________________________________                                        1302   1274           4-hydroxy-2-(6-carb-                                                          ethoxyhexyl)cyclopent-                                                        2-en-1-one                                              1303   1275           4-hydroxy-2-(6-carbo-                                                         methoxyhexyl)cyclopent-                                                       2-en-1-one                                              1304   1276           4-hydroxy-2-(4-carb-                                                          ethoxybutyl)cyclopent-                                                        2-en-1-one                                              1305   1277           4-hydroxy-2-(3-carb-                                                          ethoxypropyl)cyclopent-                                                       2-en-1-one                                              1306   1278           4-hydroxy-2-(4-carboxy-                                                       butyl)cyclopent-2-en-                                                         1-one                                                   1307   1279           4-hydroxy-2-(3-carboxy-                                                       Propyl)cyclopent-2-en-                                                        1-one                                                   1308   1281           4-hydroxy-2-(8-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                              1309   1282           4-hydroxy-2-(6-carboxy-                                                       octyl)cyclopent-2-en-                                                         1-one                                                   1310   1283           4-hydroxy-2-(6-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                              1311   1284           4-hydroxy-2-(6-carboxy-                                                       5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                    1312   1285           4-hydroxy-2-(6-carb-                                                          ethoxy-5,5-dimethyl-                                                          hexyl)cyclopent-2-en-                                                         1-one                                                   1313   1286           4-hydroxy-2-(6-carboxy-                                                       5-oxahexyl)cyclopent-                                                         2-en-1-one                                              1314   1287           4-hydroxy-2-(6-carb-                                                          ethoxy-5-oxahexyl)-                                                           cyclopent-2-en-1-one                                    1315   1288           4-hydroxy-2-(6-carboxy-                                                       6-fluorohexyl)cyclo-                                                          pent-2-en-1-one                                         1316   1289           4-hydroxy-2-(6-carb-                                                          ethoxy-6-fluorohexyl)-                                                        cyclopent-2-en-1-one                                    1317   1290           4-hydroxy-2-(5-carboxy-                                                       pentyl)cyclopent-2-en-                                                        1-one                                                   1318   1291           4-hydroxy-2-(5-carb-                                                          ethoxypentyl)cyclo-                                                           pent-2-en-1-one                                         1319   1292           4-hydroxy-2-(7-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                   1320   1293           4-hydroxy-2-(7-carb-                                                          ethoxyheptyl)cyclopent-                                                       2-en-1-one                                              1321   1294           4-hydroxy-2-(6-carboxy-                                                       6-phenylhexyl)cyclo-                                                          pent-2-en-1-one                                         1322   1295           4-hydroxy-2-(6-carb-                                                          ethoxy-6-phenylhexyl)-                                                        cyclopent-2-en-1-one                                    1323   1296           4-hydroxy-2-(6-carbo-                                                         n-butoxyhexyl)cyclo-                                                          pent-2-en-1-one                                         1324   1297           4-hydroxy-2-(6-carbo-                                                         isopropoxyhexyl)cyclo-                                                        pent-2-en-1-one                                         1325   1298           4-hydroxy-2-(6-carbo-                                                         n-decyloxyhexyl)cyclo-                                                        pent-2-en-1-one                                         1326   1299           4-hydroxy-2-(6-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                   ______________________________________                                    

EXAMPLES 1327-1337

By the procedure of Example 95, the various 4-hydroxycyclopentenones ofTable 38, which follows are converted to the tetrahydropyranyl4-tetrahydropyranyloxycyclopentenone esters of the table.

                  Table 38                                                        ______________________________________                                               Starting 4-hy- Product Tetrahydropyran-                                Ex-    droxycyclopenten-                                                                            2'-yl 4-tetrahydropy-                                   ample  one of Example ran-2'-yl-oxycyclopent-                                                       2-en-1-ones                                             ______________________________________                                        1327   1306           4-tetrahydropyran-2'-                                                         yloxy-2-(4-carbotetra-                                                        hydropyran-2'-yloxy-                                                          butyl)cyclopent-2-en-1-                                                       one                                                     1328   1307           4-tetrahydropyran-2'-                                                         yloxy-2-(3-carbotetra-                                                        hydropyran-2'-yloxy-                                                          propyl)cyclopent-2-en-                                                        1-one                                                   1329   1300           4-tetrahydropyran-2'-                                                         yloxy-2-(8-carbotetra-                                                        hydropyran-2'-yloxy-                                                          octyl)cyclopent-2-en-1-                                                       one                                                     1330   1309           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          octyl)cyclopent-2-en-1-                                                       one                                                     1331   1311           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                    1332   1313           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-5-                                                        oxahexyl)cyclopent-2-                                                         en-1-one                                                1333   1315           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-6-                                                        fluorohexyl)cyclopent-                                                        2-en-1-one                                              1334   1317           4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbotetra-                                                        hydropyran-2'-yloxy-                                                          pentyl)cyclopent-2-en-1-                                                      one                                                     1335   1319           4-tetrahydropyran-2'-                                                         yloxy-2-(7-carbotetra-                                                        hydropyran-2'-yloxyhep-                                                       tyl)cyclopent-2-en-1-                                                         one                                                     1336   1321           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-6-                                                        phenylhexyl)cyclopent-                                                        2-en-1-one                                              1337   1326           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          heptyl)cyclopent-2-en-                                                        1-one                                                   ______________________________________                                    

EXAMPLE 1338 Preparation of4-tetrahydropyranyloxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 674 mg. (2.64 mmoles) of4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1302) and2.22 g. (26.4 mmoles) of dihydropyran in 2.6 ml. of methylene chlorideis added 5.0 mg.(0.026 mmoles) of p-toluenesulfonic acid monohydrate.After stirring for 20 minutes at room temperature the solution isdiluted with ether and poured into saturated sodium chloride solutioncontaining a little sodium bicarbonate. The organic phase is separatedand washed with saturated sodium chloride solution. The extract is driedover magnesium sulfate, and volatile matter is evaporated at reducedpressure to give an oil, λ_(max).^(MeOH) = 224 mμ (7950); max. = 1735(ester carbonyl group), 1710 (ketone carbonyl group), and 1030 cm⁻ ¹(tetrahydropyranyloxy group).

EXAMPLE 1339-1352

In the manner of Example 1338 the alkyl 4-hydroxycyclopentenone estersof Table 39, which follows, are converted to the corresponding4-tetrahydropyranyloxy alkyl esters of the table.

                  TABLE 39                                                        ______________________________________                                               Starting 4-                                                                   hydroxycyclo-  4-tetrahydropyran-                                      Ex-    pentenone Esters                                                                             2'yloxycyclopent-                                       ample  of Example     2-en-1-one esters                                       ______________________________________                                        1339   1303           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbomethoxy-                                                      hexyl)cyclopent-2-en-1-                                                       one                                                     1340   1304           4-tetrahydropyran-2'-                                                         yloxy-2-(4-carbethoxy-                                                        butyl)cyclopent-2-en-1-                                                       one                                                     1341   1305           4-tetrahydropyran-2'-                                                         yloxy-2-(3-carbethoxy-                                                        propyl)cyclopent-2-en-1-                                                      one                                                     1342   1308           4-tetrahydropyran-2'-                                                         yloxy-2-(8-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                     1343   1310           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                     1344   1312           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-5,                                                      5-dimethylhexyl)cyclo-                                                        pent-2-en-1-one                                         1345   1314           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-5-                                                      oxahexyl)cyclopent-2-en-                                                      1-one                                                   1346   1316           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-6-                                                      fluorohexyl)cyclopent-                                                        2-en-1-one                                              1347   1318           4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbethoxy-                                                        pentyl)cyclopent-2-en-                                                        1-one                                                   1348   1320           4-tetrahydropyran-2'-                                                         yloxy-2-(7-carbethoxy-                                                        heptyl)cyclopent-2-en-1-                                                      one                                                     1349   1322           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-6-                                                      phenylhexyl)cyclopent-2-                                                      en-1-one                                                1350   1323           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-                                                           butoxyhexyl)cyclopent-2-                                                      en-1-one                                                1351   1324           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-iso-                                                         propoxyhexyl)cyclopent-                                                       2-en-1-one                                              1352   1325           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-dec-                                                       yloxyhexyl)cyclopent-2-                                                       en-1-one                                                ______________________________________                                    

EXAMPLE 1353 Preparation of 8β-methyl-prostaglandin E₁,8α-methyl-8-iso-prostaglandin E₁,8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid, and8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic acid

The Grignard reagent, prepared as described in Example 1187 from 1.54 g.of magnesium, 22.5 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728), and 30 ml. of tetrahydrofuran, is added to a ice cooledsolution of 17.75 g. of11-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxyhexyl)-2-cyclopentenone(Example 95 ) and 1.25 g. of copper (I) iodide-tri-n-butylphosphinecomplex in 30 ml. of tetrahydrofuran over 15 minutes under an inertatmosphere. The mixture is stirred with cooling for 0.5 hour. To themixture is then added 100 g. of methyl iodide, the cooling bath is thenremoved and the mixture is stirred at ambient temperatures for 48 hours.The mixture is then poured into ice cold saturated ammonium chloridesolution and the layers are separated. The aqueous phase is washed withether and combined organic phase and washings are washed with saturatedbrine, and evaporated in vacuo. The residue is heated to 45°C. for 5hours with 840 ml. of 4:2:1 tetrahydrofuran-acetic acid-water under aninert atmosphere and is then evaporated to dryness in vacuo. The residueis chromatographed upon Silic AR CC-4 using a benzene-ethyl acetategradient as eluent to yield the title compounds as a mixture of8β-methyl-protaglandin E₁ and 8α-methyl-8-iso-prostaglandin E₁ and amixture of 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid and8α-methyl-9-oxo-11α,15-dihydroxy 8-iso-cis-8α isomers; resolution of themixtures is then accomplished by a combination of partitionchromatography and thin-layer chromatography.

EXAMPLES 1354-1386

Treatment of the blocked 4-oxycyclopent-2-en-1-ones listed in Table 40below by the procedure described in Example 1353 with the Grignardreagents, prepared by the procedure described in Example 1187 from thelisted 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyliodide furnishes the product 8α- and 8β-methyl prostenoates of thetable. The products of Examples 1354-1378 inclusive are initiallyobtained as the corresponding15-O-triphenylmethyl-11-O-tetrahydropyranyl tetrahydropyranyl esters.These blocking groups are then cleaved by the procedure described inExample 1353 by treatment at 45°C. for five hours with 4:2:1tetrahydrofuran:acid:water. The alkyl esters products of Examples1379-1385 inclusive are obtained initially as the corresponding15-O-triphenylmethyl-11-O-tetrahydropyranyl derivatives. These 11- and15-hydroxy blocking groups are then cleaved by the deblocking proceduredescribed in Example 1353. The products of Example 1386 are initiallyobtained as the corresponding 15-O-triphenylmethyl derivatives, whichare cleaved hydrolytically to the listed free 15-ols by the processdescribed in Example 1353.

                                      TABLE 40                                    __________________________________________________________________________    Ex- Starting blocked                                                                       Starting 1-bromo-                                                ample                                                                             4-oxycyclopent-                                                                        3-triphenylmethoxy-                                                  2-en-1-one of                                                                          1-trans-alkene of                                                    Example  Example    Product 8-methylprostenoic acid                       __________________________________________________________________________    1354                                                                               95      1175       8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            N                                                                             dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-16,16                            -                                                                             dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            Z                                                                             dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-16,16                            -                                                                             dimethyl-8-iso-13-cis-prostenoic acid                 1355                                                                               95      1178       8β-methyl-9-oxo-11α,15-dihydroxy,17,17-                            '                                                                             dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-17,17                            -                                                                             dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-17,17-                            4                                                                             dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-17,17                            -                                                                             dimethyl-8-iso-13-cis-prostenoic acid                 1356                                                                               95      1182       8β-methyl-9-oxo-11α,15-dihydroxy-13-tra                            ns,                                                                           17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-8-iso                            -13-                                                                          trans,17-cis-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-13-cis                            ,                                                                             17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-8-iso                            -13-                                                                          cis,17-cis-prostadienoic acid                         1357                                                                               95      1185       8β-methyl-9-oxo-11α,15-dihydroxy-20-eth                            yl-                                                                           13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-20-et                            hyl-                                                                          8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-20-eth                            yl-                                                                           13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-20-et                            hyl-                                                                          8-iso-13-cis-prostenoic acid                          1358                                                                              1327      728       8β-methyl-9-oxo-11α,15-dihydroxy-6,7-di                            nor-                                                                          13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-6,7-d                            inor-                                                                         8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-6,7-di                            nor-                                                                          13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-6,7-d                            inor-                                                                         8-iso-13-cis-prostenoic acid                          1359                                                                              1328     1186       8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                            tri-                                                                          nor-20-methyl-13-trans-prostenoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7                            -tri-                                                                         nor-20-methyl-8-iso-13-trans-prostenoic acid                                  8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                            tri-                                                                          nor-20-methyl-13-cis-prostenoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7                            -tri-                                                                         nor-20-methyl-8-iso-13-cis-prostenoic acid            1360                                                                              1329      728       8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                            bis-                                                                          homo-13-trans-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b                            -bis-                                                                         homo-8-iso-13-trans-prostenoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                            bis-                                                                          homo-13-cis-prostenoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b                            -bis-                                                                         homo-8-iso-13-cis-prostenoic acid                     1361                                                                              1330      728       8β-methyl-9-oxo-11α,15-dihydroxy-2-ethy                            l-13-                                                                         trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-eth                            yl-8-                                                                         iso-13-trans-prostenoic acid                                                  8β-methyl-9-oxo-11α,15-dihydroxy-2-ethy                            l-13-                                                                         cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-2-eth                            yl-8-                                                                         iso-13-cis-prostenoic acid                            1362                                                                              1331     1186       8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20                            -tri-                                                                         methyl-13-trans-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3,3,2                            0-tri-                                                                        methyl-8-iso-13-trans-prostenoic acid                                         8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20                            -tri-                                                                         methyl-13-cis-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,2                            0-tri-                                                                        methyl-8-iso-13-cis-prostenoic acid                   1363                                                                              1332      728       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            13-                                                                           trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -8-iso-                                                                       13-trans-prostenoic acid                                                      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            13-                                                                           cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -8-                                                                           iso-13-cis-prostenoic acid                            1364                                                                              1332     1175       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            16,16-                                                                        dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -16,16-                                                                       dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            16,16-                                                                        dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -16,16-                                                                       dimethyl-8-iso-13-cis-prostenoic acid                 1365                                                                              1332     1182       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            13-                                                                           trans,17-cis-prostadienoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -8-iso-                                                                       13-trans,17-cis-prostadienoic acid                                            8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            13-                                                                           cis,17-cis-prostadienoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -8-iso-                                                                       13-cis,17-cis-prostadienoic acid                      1366                                                                              1332     1185       8β -methyl-oxo-11α,15-dihydroxy-3-oxa-2                            0-                                                                            ethyl-13-trans-prostenoic acid                                                8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -20-                                                                          ethyl-8-iso-13-trans-prostenoic acid                                          8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                            20-                                                                           ethyl-13-cis-prostenoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa                            -20-                                                                          ethyl-8-iso-13-cis-prostenoic acid                    1367                                                                              1333     1178       8β-methyl-9-oxo-11α,15-dihydroxy-2-fluo                            ro-                                                                           17,17-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-2-flu                            oro-                                                                          17,17-dimethyl-8-iso-13-trans-prostenoic acid                                 8β-methyl-9-oxo-11α,15-dihydroxy-2-fluo                            ro-                                                                           17,17-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-flu                            oro-                                                                          17,17-dimethyl-8-iso-13-cis-prostenoic acid           1368                                                                              1334      728       8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-                            13-                                                                           trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-7-nor                            -8-                                                                           iso-13-trans-prostenoic acid                                                  8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-                            13-                                                                           cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-7-nor                            -8-                                                                           iso-13-cis-prostenoic acid                            1369                                                                              1335     1175       8β-methyl-9-oxo-11α,15-dihydroxy-7a-hom                            o-                                                                            16,16-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-7a-ho                            mo-16,16-                                                                     dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-7a-hom                            o-                                                                            16,16-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-7a-ho                            mo-                                                                           16,16-dimethyl-8-iso-13-cis-prostenoic acid           1370                                                                              1336      728       8β-methyl-9-oxo-11α,15-dihydroxy-2-phen                            yl-                                                                           13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-2-phe                            nyl-                                                                          8-iso-13-trans-prostenoic acid                                                8β -methyl-9-oxo-11α,15-dihydroxy-2-phe                            nyl-                                                                          13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-2-phe                            nyl-                                                                          8-iso-13-cis-prostenoic acid                          1371                                                                              1337     1182       8β-methyl-9-oxo-11α,15-dihydroxy-2-meth                            yl-                                                                           13-trans,17-cis-prostadienoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-2-met                            hyl-                                                                          8-iso-13-trans,17-cis-prostadienoic acid                                      8β-methyl-9-oxo-11α,15-dihydroxy-2-meth                            yl-                                                                           13-cis,17-cis-prostadienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-2-met                            hyl-                                                                          8-iso-13-cis,17-cis-prostadienoic acid                1372                                                                              1121      728       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            13-                                                                           trans-prostadienoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-8-iso                            -5-                                                                           cis,13-trans-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            13-                                                                           cis-prostadienoic acid                                                        8α-methyl-9-oxo-11α                                               ,15-dihydroxy-8-iso-5-                                                        cis,13-cis-prostadienoic acid                         1373                                                                              1121     1182       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            13-                                                                           trans,17-cis-prostatrienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-8-iso                            -5-                                                                           cis,13-trans,17-cis-prostatrienoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            1                                                                             13-cis,17-cis-prostatrienoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-8-iso                            -                                                                             5-cis,13-cis,17-cis-prostatrienoic acid               1374                                                                              1121     1175       8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            di-                                                                           methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-16,16                            -di-                                                                          methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            di-                                                                           methyl-5-cis,13-cis-prostadienoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-16,16                            -di-                                                                          methyl-8-iso-5-cis,13-cis-prostadienoic acid          1375                                                                              1122     1186       8β -methyl-9-oxo-11α,15-dihydroxy-4-nor                            -20-                                                                          methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-4-nor                            -20-                                                                          methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-                            20-                                                                           methyl-5-cis,13-cis-prostadienoic acid                                        8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-                            20-                                                                           methyl-8-iso-5-cis,13-cis-prostadienoic acid          1376                                                                              1123     1178       8β-methyl-9-oxo-11α,15-dihydroxy-4a-hom                            o-17,                                                                         17-dimethyl-5-cis,13-trans-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a-ho                            mo-17,                                                                        17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                                          8β-methyl-9-oxo-11α,15-dihydroxy-4a-hom                            o-17,                                                                         17-dimethyl-5-cis,13-cis-prostadienoic acid                                   8α-methyl-9-oxo-11α,15-dihydroxy-4a-ho                            mo-17,                                                                        17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                  1377                                                                              1124     1185       8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                            bis-                                                                          homo-20-ethyl-5-cis,13-trans-prostadienoic                                    acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b                            -bis-                                                                         homo-20-ethyl-8-iso-5-cis,13-trans-prosta-                                    dienoic acid                                                                  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                            bis-                                                                          homo-20-ethyl-5-cis,13-cis-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b                            -bis-                                                                         homo-20-ethyl-8-iso-5-cis,13-cis-prosta-                                      dienoic acid                                          1378                                                                              1124     1182       8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                            bis-                                                                          homo-5-cis,13-trans,17-cis-prostatrienoic                                     acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b                            -bis-                                                                         homo-8-iso-5-cis,13-trans,17-cis-prosta-                                      trienoic acid                                                                 8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                            bis-                                                                          homo-5-cis,13-cis,17-cis-prostatrienoic acid                                  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b                            -bis-                                                                         homo-8-iso-5-cis,13-cis-17-cis-prostatrienoic                                 acid                                                  1379                                                                              1339     1186       Methyl 8β -methyl-9-oxo-11α,15-dihydrox                            y-20-                                                                         methyl-13-trans-prostenoate                                                   Methyl 8α-methyl-9-oxo-11α,15-dihydrox                            y-20-                                                                         methyl-8-iso-13-trans-prostenoate                                             Methyl 8β-methyl-9-oxo-11a,15-dihydroxy-20-                              methyl-13-cis-prostenoate                                                     Methyl 8α-methyl-9-oxo-11α,15-dihydrox                            y-20-                                                                         methyl-8-iso-13-cis-prostenoate                       1380                                                                              1342     1182       Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            7a,7b-                                                                        bishomo-13-trans,17-cis-prostadienoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -7a,7b-                                                                       bishomo-8-iso-13-trans,17-cis-prostadienoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            7a,7b-                                                                        bishomo-13-cis,17-cis-prostadienoate                                          Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -7a,7b-                                                                       bishomo-8-iso-13-cis,17-cis-prostadienoate            1381                                                                              1343     1175       Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            2-                                                                            ethyl-16,16-dimethyl-13-trans-prostenoate                                     Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -2-                                                                           ethyl-16-16-dimethyl-8-iso-13-trans-                                          prostenoate                                                                   Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            2-                                                                            ethyl-16,16-dimethyl-13-cis-prostenoate                                       Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -2-                                                                           ethyl-16,16-dimethyl-8-iso-13-cis-prostenoate         1382                                                                              1344     1178       Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            3,3-                                                                          17,17-tetramethyl-13-trans-prostenoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -3,3-                                                                         17,17-tetramethyl-8-iso-13-trans-prostenoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            3,3-                                                                          17,17-tetramethyl-13,cis-prostenoate                                          Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -3,3-                                                                         17,17-tetramethyl-8-iso-13-cis-prostenoate            1383                                                                              1345     1178       Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            3-oxa-                                                                        17,17-dimethyl-13-trans-prostenoate                                           Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -3-oxa-                                                                       17,17-dimethyl-8-iso-13-trans-prostenoate                                     Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            3-oxa-                                                                        17,17-dimethyl-13-cis-prostenoate                                             Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -3-oxa-                                                                       17,17-dimethyl-8-iso-13-cis-prostenoate               1384                                                                              1350      728       Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            13-                                                                           trans-prostenoate                                                             Butyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -8-iso-                                                                       13-trans-prostenoate                                                          Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            13-                                                                           cis-prostenoate                                                               Butyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -8-iso-                                                                       13-cis-prostenoate                                    1385                                                                              1352     1182       Decyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            t                                                                             13-trans,17-cis-prostadienoate                                                Decyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -8-iso-                                                                       13-trans,17-cis-prostadienoate                                                Decyl 8β-methyl-oxo-11α,15-dihydroxy-13                            -                                                                             cis-17-cis-prostadienoate                                                     Decyl 8α-methyl-9-oxo-11α,15-dihydroxy                            -8-iso-                                                                       13-cis,17-cis-prostadienoate                          1386                                                                              1301      728       Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hy                            droxy-                                                                        13-trans-prostenoate                                                          Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-h                            ydroxy-                                                                       8-iso-13-trans-prostenoate                                                    Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hy                            droxy-                                                                        13-cis-prostenoate                                                            Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-h                            ydroxy-                                                                       8-iso-13-cis-prostenoate                              __________________________________________________________________________

EXAMPLE 1387 Preparation of 8β-methyl-prostaglandin A₁

A mixture of 0.30 g. of 8β-methyl-prostaglandin E₁ (Example 1353) and 10ml. of 1:9 aqueous acetic acid is heated to 65°C. for 18 hours under aninert atmosphere. The solvent is removed in vacuo and the residue ispurified upon Silic AR-CC-4 using a benzene-ethylacetate gradient toyield the title compound.

EXAMPLES 1388-1522

Treatment of the designated 8-methyl-9-oxo-11-hydroxy-prostenoic acidderivatives of Table 41 below with 1:9 aqueous acid and purification allas described in Example 1387 gives the corresponding8-methyl-9-oxo-10,13-prostadienoic acids and esters of the table.

                  TABLE 41                                                        ______________________________________                                               Starting 9-oxo-                                                                             Product 8-methyl-9-oxo-                                  Exam-  11-hydroxy    10,13-prostadienoic                                      ple    derivative    acids or esters                                          ______________________________________                                        1388   8α-methyl-8-iso-                                                                     8α-methyl-8-prosta-                                        prostaglandin                                                                              glandin A.sub.1                                                  E.sub.1 (Example 1353)                                                 1389   8β-methyl-9-oxo-                                                                      8β-methyl-11α,15-dihy-                                11α,15-dihy-                                                                         droxy-10,13-cis-prosta-                                          droxy-13-cis-                                                                              dienoic acid                                                     prostenoic acid                                                               (Example 1353)                                                         1390   8α-methyl-9-oxo-                                                                     8α-methyl-11α,15-dihy-                               11α,15-dihy-                                                                         droxy-8-iso-10,13-cis-                                           droxy-8-iso-13-                                                                            prostadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1353)                                                                  1391   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihy-                                                                         droxy-16,16-dimethyl                                             droxy-16,16-di-                                                                            10,13-trans-prostadie-                                           methyl-13-trans-                                                                           noic acid                                                        prostenoic acid                                                               (Example 1354)                                                         1392   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihy-                                                                         droxy-16,16-dimethyl-                                            droxy-16,16-di-                                                                            8-iso-10,13-trans-pro-                                           methyl-8-iso-13-                                                                           stadienoic acid                                                  trans-proste-                                                                 noic acid (Exam-                                                              ple 1354)                                                              1393   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-16,16-dimethyl                                             xy-16,16-di- 10,13-cis-prostadienoic                                          methyl-13-cis-                                                                             acid                                                             prostenoic acid                                                               (Example 1354)                                                         1394   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-16,16-dimethyl-                                            xy-16,16-di-                                                           8-iso-10,13-cis-pro-                                                                 methyl-8-iso-13-                                                                           stadienoic acid                                                  cis-prostenoic                                                                acid (Example                                                                 1354)                                                                  1395   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-17,17-dimethyl                                             xy-17,17-di- 10,13-trans-prostadie-                                           methyl 13-trans-                                                                           noic acid                                                        prostenoic acid                                                               (Example 1355)                                                         1396   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-17,17-dimethyl-                                            xy-17,17-di- 8-iso-10,13-trans-pro-                                           methyl-8-iso-13-                                                                           stadienoic acid                                                  trans-prostenoic                                                              acid (Example                                                                 1355)                                                                  1397   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-17,17-dimethyl                                             xy-17,17-di- 10,13-cis-prostadie-                                             methyl 13-cis-                                                                             noic acid                                                        prostenoic acid                                                               (Example 1355)                                                         1398   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-17,17-dimethyl-                                            xy-17,17-di- 8-iso-10,13-cis-pro-                                             methyl-8-iso-13-                                                                           stadienoic acid                                                  cis-prostenoic                                                                acid (Example                                                                 1355)                                                                  1399   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-10,13-trans,17-                                            xy-13-trans,17-                                                                            cis-prostatrienoic                                               cis-prostadi-                                                                              acid                                                             enoic acid                                                                    (Example 1356)                                                         1400   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-10,13-trans,-                                        xy-8-iso-13- 17-cis-prostatrienoic                                            trans,17-cis-                                                                              acid                                                             prostadienoic                                                                 acid (Example                                                                 1356)                                                                  1401   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-10,13-cis,17-cis-                                          xy-13-cis,17-cis-                                                                          prostatrienoic acid                                              prostadienoic                                                                 acid (Example                                                                 1356)                                                                  1402   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-10,13-cis,-                                          xy-8-iso-13-cis,-                                                                          17-cis-prostatrienoic                                            17-cis-prostadi-                                                                           acid                                                             enoic acid                                                                    (Example 1356)                                                         1403   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-20-ethyl-10,13-                                            xy-20-ethyl-13-                                                                            trans-prostadienoic                                              trans-proste-                                                                              acid                                                             noic acid (Exam-                                                              ple 1357)                                                              1404   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-20-ethyl-8-iso-                                            xy-20-ethyl-8-                                                                             10,13-trans-prostadi-                                            iso-13-trans-                                                                              enoic acid                                                       prostenoic acid                                                               (Example 1357)                                                         1405   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α ,15-dihydro-                                                                     droxy-20-ethyl-10,13-                                            xy-20-ethyl-13-                                                                            cis-prostadienoic acid                                           cis-prostenoic                                                                acid (Example                                                                 1357)                                                                  1406   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-20-ethyl-8-iso-                                            xy-20-ethyl-8-                                                                             10,13-cis-prostadie-                                             iso-13-cis-pro-                                                                            noic acid                                                        stenoic acid                                                                  (Example 1357)                                                         1407   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-6,7-dinor-10,13-                                           xy-6,7-dinor-13-                                                                           trans-prostadienoic                                              trans-proste-                                                                              acid                                                             noic acid (Exam-                                                              ple 1358)                                                              1408   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-6,7-dinor-8-iso-                                           xy-6,7-dinor-8-                                                                            10,13-trans-prostadie-                                           iso-13-trans-                                                                              noic acid                                                        prostenoic acid                                                               (Example 1358)                                                         1409   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-6,7-dinor-10,13-                                           xy-6,7-dinor-13-                                                                           cis-prostadienoic acid                                           cis-prostenoic                                                                acid (Example                                                                 1358)                                                                  1410   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-6,7-dinor-8-iso-                                           xy-6,7-dinor-8-                                                                            10,13-cis-prostadie-                                             iso-13-cis-pro-                                                                            noic acid                                                        stenoic acid                                                                  (Example 1358)                                                         1411   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-5,6,7-trinor-20-                                           xy-5,6,7-trinor-                                                                           methyl 10,13-trans-                                              20-methyl 13-                                                                              prostadienoic acid                                               trans-prostenoic                                                              acid (Example                                                                 1359)                                                                  1412   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-5,6,7-trinor-20-                                           xy-5,6,7-trinor-                                                                           methyl-8-iso-10,13-                                              20-methyl-8-iso-                                                                           trans-prostadienoic                                              13-trans-pro-                                                                              acid                                                             stenoic acid                                                                  (Example 1359)                                                         1413   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-5,6,7-trinor-20-                                           xy-5,6,7-trinor-                                                                           methyl 10,13-cis-pro-                                            20-methyl 13-                                                                              stadienoic acid                                                  cis-prostenoic                                                                acid (Example                                                                 1359)                                                                  1414   8α-methyl-9-oxo-                                                                     8α -methyl-9-oxo-15-hy-                                    11α,15-dihydro-                                                                      droxy-5,6,7-trinor-20-                                           xy-5,6,7-trinor-                                                                           methyl-8-iso-10,13-                                              20-methyl-8- cis-prostadienoic acid                                           iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1359)                                                         1415   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7a,7b-bishomo-                                             xy-7a,7b-bishomo-                                                                          10,13-trans-prostadie-                                           13-trans-pro-                                                                              noic acid                                                        stenoic acid                                                                  (Example 1360)                                                         1416   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-7a,7b-bishomo-                                             xy-7a,7b-bishomo                                                                           8-iso-10,13-trans-                                               8-iso-13-trans-                                                                            prostadienoic acid                                               prostenoic acid                                                               (Example 1360)                                                         1417   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7a,7b-bishomo-                                             xy-7a,7b-bishomo-                                                                          10,13-cis-prostadie-                                             13-cis-proste-                                                                             noic acid                                                        noic acid (Exam-                                                              ple 1360)                                                              1418   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-7a,7b-bishomo-                                             xy-7a,7b-bishomo-                                                                          8-iso-10,13-cis-pro-                                             8-iso-13-cis-                                                                              stadienoic acid                                                  prostenoic acid                                                               (Example 1360)                                                         1419   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-ethyl-10,13-                                             xy-2-ethyl-13-                                                                             trans-prostadienoic                                              trans-proste-                                                                              acid                                                             noic acid (Exam-                                                              ple 1361)                                                              1420   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-ethyl-8-iso-                                             xy-2-ethyl-8-                                                                              10,13-trans-prostadi-                                            iso-13-trans-                                                                              enoic acid                                                       prostenoic acid                                                               (Example 1361)                                                         1421   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-ethyl-10,13-                                             xy-2-ethyl-13-                                                                             cis-prostadienoic acid                                           cis-prostenoic                                                                acid (Example                                                                 1361)                                                                  1422   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-ethyl-8-iso-                                             xy-2-ethyl-8-                                                                              10,13-cis-prostadie-                                             iso-13-cis-pro-                                                                            noic acid                                                        stenoic acid                                                                  (Example 1361)                                                         1423   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3,3,20-trimethyl-                                          xy-3,3,20-tri-                                                                             10,13-trans-prostadi-                                            methyl-13-trans-                                                                           enoic acid                                                       prostenoic acid                                                               (Example 1362)                                                         1424   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3,3,20-trimethyl-                                          xy-3,3,20-tri-                                                                             8-iso-10,13-trans-pro-                                           methyl-8-iso-13-                                                                           stadienoic acid                                                  trans-proste-                                                                 noic acid                                                                     (Example 1362)                                                         1425   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3,3,20-trimethyl-                                          xy-3,3,20-tri-                                                                             10,13-cis-prostadie-                                             methyl-13-cis-                                                                             noic acid                                                        prostenoic acid                                                               (Example 1362)                                                         1426   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3,3,20-trimethyl-                                          xy-3,3,20-tri-                                                                             8-iso-10,13-cis-pro-                                             methyl-8-iso-13-                                                                           stadienoic acid                                                  cis-prostenoic                                                                acid (Example                                                                 1362)                                                                  1427   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-10,13-trans-                                         xy-3-oxa-13- prostadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1363)                                                              1428   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-8-iso-10,-                                           xy-3-oxa-8-iso-                                                                            13,trans-prostadienoic                                           13-trans-proste-                                                                           acid                                                             noic acid (Exam-                                                              ple 1363)                                                              1429   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-10,13-cis-                                           xy-3-oxa-13-cis-                                                                           prostadienoic acid                                               prostenoic acid                                                               (Example 1363)                                                         1430   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-8-iso-10,-                                           xy-3-oxa-8-iso-                                                                            13-cis-prostadienoic                                             13-cis-proste-                                                                             acid                                                             noic acid (Exam-                                                              ple 1363)                                                              1431   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-16,16-di-                                            xy-3-oxa-16,16-                                                                            methyl-10,13-trans-pro-                                          dimethyl-13- stadienoic acid                                                  trans-proste-                                                                 noic acid (Exam-                                                              ple 1364)                                                              1432   8α-methyl-9-oxo-                                                                     8α -methyl-9-oxo-15-hy-                                    11α,15-dihydro-                                                                      droxy-3-oxa-16,16-di-                                            xy-3-oxa-16,16-                                                                            methyl-8-iso-10,13-                                              dimethyl-8-iso-                                                                            trans-prostadienoic                                              13-trans-proste-                                                                           acid                                                             noic acid (Exam-                                                              ple 1364)                                                              1433   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-16,16-di-                                            xy-3-oxa-16,16-                                                                            methyl-10,13-cis-pro-                                            dimethyl-13-cis-                                                                           stadienoic acid                                                  prostenoic acid                                                               (Example 1364)                                                         1434   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-16,16-di-                                            xy-3-oxa-16,16-                                                                            methyl-8-iso-10,13-cis-                                          dimethyl-8-iso-                                                                            prostadienoic acid                                               13-cis-proste-                                                                noic acid (Exam-                                                              ple 1364)                                                              1435   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-10,13-                                               xy-3-oxa-13- trans,17-cis-prosta-                                             trans,17-cis-                                                                              trienoic acid                                                    prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1436   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-8-iso-10,-                                           xy-3-oxa-8-iso-                                                                            13-trans,17-cis-pro-                                             13-trans,17-cis-                                                                           statrienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1437   8β-methy;-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-10,13-cis,-                                          xy-3-oxa-13-cis,-                                                                          17-cis-prostatrienoic                                            17-cis-prosta-                                                                             acid                                                             dienoic acid                                                                  (Example 1365)                                                         1438   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-8-iso-10,-                                           xy-3-oxa-8-iso-                                                                            13-cis,17-cis-prosta-                                            13-cis,17-cis-                                                                             trienoic acid                                                    prostadienoic                                                                 acid (Example                                                                 1365)                                                                  1439   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-20-ethyl-                                            xy-3-oxa-20- 10,13-trans-prostadie-                                           ethyl-13-trans-                                                                            noic acid                                                        prostenoic acid                                                               (Example 1366)                                                         1440   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-20-ethyl-                                            xy-3-oxa-20- 8-iso-10,13-trans-                                               ethyl-8-iso-13-                                                                            prostadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1366)                                                              1441   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-3-oxa-20-ethyl-                                            xy-3-oxa-20- 10,13-cis-prostadie-                                             ethyl-13-cis-                                                                              noic acid                                                        prostenoic acid                                                               (Example 1366)                                                         1442   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-3-oxa-20-ethyl-                                            xy-3-oxa-20- 8-iso-10,13-cis-pro-                                             ethyl-8-iso-13-                                                                            stadienoic acid                                                  cis-prostenoic                                                                acid (Example                                                                 1366)                                                                  1443   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-fluoro-17,17-                                            xy-2-fluoro-17,-                                                                           dimethyl-10,13-trans-                                            17-dimethyl-13-                                                                            prostadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1367)                                                              1444   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-fluoro-17,17-                                            xy-2-fluoro-17,-                                                                           dimethyl-8-iso-10,13-                                            17-dimethyl-8-                                                                             trans-prostadienoic                                              iso-13-trans-                                                                              acid                                                             prostenoic acid                                                               (Example 1367)                                                         1445   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-fluoro-17,17-                                            xy-2-fluoro-17,-                                                                           dimethyl-10,13-cis-                                              17-dimethyl-13-                                                                            prostadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1367)                                                                  1446   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-fluoro-17,17-                                            xy-2-fluoro-17,-                                                                           dimethyl-8-iso-10,13-                                            17-dimethyl-8-                                                                             cis-prostadienoic acid                                           iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1367)                                                         1447   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7-nor-10,13-trans-                                         xy-7-nor-13- prostadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1368)                                                              1448   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-7-nor-8-iso-10,-                                           xy-7-nor-8-iso-                                                                            13-trans-prostadienoic                                           13-trans-pro-                                                                              acid                                                             stenoic acid                                                                  (Example 1368)                                                         1449   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7-nor-10,13-cis-                                           xy-7-nor-13-cis-                                                                           prostadienoic acid                                               prostenoic acid                                                               (Example 1368)                                                         1450   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-7-nor-8-iso-10,-                                           xy-7-nor-8-iso-                                                                            13-cis-prostadienoic                                             13-cis-proste-                                                                             acid                                                             noic acid (Exam-                                                              ple 1368)                                                              1451   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7a-homo-16,16-                                             xy-7a-homo-16,-                                                                            dimethyl-10,13-trans-                                            16-dimethyl-13-                                                                            prostadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1369)                                                              1452   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihyro-                                                                       droxy-7a-homo-16,16-                                             xy-7a-homo-16,-                                                                            dimethyl-8-iso-10,13-                                            16-dimethyl-8-                                                                             trans-prostadienoic                                              iso-13-trans-                                                                              acid                                                             prostenoic acid                                                               (Example 1369)                                                         1453   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-7a-homo-16,16-                                             xy-7a-homo-16,-                                                                            dimethyl-10,13-cis-                                              16-dimethyl-13-                                                                            prostadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1369)                                                                  1454   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-7a-homo-16,16-                                             xy-7a-homo-16,-                                                                            dimethyl-8-iso-10,13-                                            16-dimethyl-8-                                                                             cis-prostadienoic acid                                           iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1369)                                                         1455   8β-methyl-9-oxo-                                                                      8β -methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-phenyl-10,13-                                            xy-2-phenyl-13-                                                                            trans-prostadienoic                                              trans-prostenoic                                                                           acid                                                             acid (Example                                                                 1370)                                                                  1456   8α-methyl-9-oxo-                                                                     8α-methy-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-phenyl-8-iso-                                            xy-2-phenyl-8-                                                                             10,13-trans-prostadi-                                            iso-13-trans-                                                                              enoic acid                                                       prostenoic acid                                                               (Example 1370)                                                         1457   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy                                       11α,15-dihydro-                                                                      droxy-2-phenyl-10,13-                                            xy-2-phenyl-13-                                                                            cis-prostadienoic acid                                           cis-prostenoic                                                                acid (Example                                                                 1370)                                                                  1458   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-phenyl-8-iso-                                            xy-2-phenyl-8-                                                                             10,13-cis-prostadie-                                             iso-13-cis-pro-                                                                            noic acid                                                        stenoic acid                                                                  (Example 1370)                                                         1459   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-methyl-10,13-                                            xy-2-methyl-13-                                                                            trans,17-cis-prosta-                                             trans,17-cis-                                                                              trienoic acid                                                    prostadienoic                                                                 acid (Example                                                                 1371)                                                                  1460   8α-methyl-9-oxo-                                                                     8αmethyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-methyl-8-iso-                                            xy-2-methyl-8-                                                                             10,13-trans,17-cis-                                              iso-13-trans,-                                                                             prostatrienoic acid                                              17-cis-prostadi-                                                              enoic acid                                                                    (Example 1371)                                                         1461   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-2-methyl-10,13-                                            xy-2-methyl-13-                                                                            cis,17-cis-prostatri-                                            cis,17-cis-pro-                                                                            enoic acid                                                       stadienoic acid                                                               (Example 1371)                                                         1462   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-2-methyl-8-iso-                                            xy-2-methyl-8-                                                                             10,13-cis,17-cis-pro-                                            iso-13-cis,17-                                                                             statrienoic acid                                                 cis-prostadie-                                                                noic acid (Exam-                                                              ple 1371)                                                              1463   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11β,15-dihydro-                                                                       droxy-5,cis,10,13-trans-                                         xy-5,cis,13- prostatrienoic acid                                              trans-prosta-                                                                 dienoic acid                                                                  (Example 1372)                                                         1464   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-5,cis,10-                                            xy-8-iso-5,cis,-                                                                           13-trans-prostatrienoic                                          13-trans-prosta-                                                                           acid                                                             dienoic acid                                                                  (Example 1372)                                                         1465   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-5,cis,10,13-cis-                                           xy-5,cis,13-cis-                                                                           prostatrienoic acid                                              prostadienoic                                                                 acid (Example                                                                 1372)                                                                  1466   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-5,cis,10,13-                                         xy-8-iso-5,cis,-                                                                           cis-prostatrienoic acid                                          13-cis-prostadi-                                                              enoic acid                                                                    (Example 1372)                                                         1467   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-5-cis,10,13-                                               xy-5-cis,13- trans,17-cis-prosta-                                             trans,17-cis-                                                                              tetraeneoic acid                                                 prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1468   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-5-cis,10,-                                           xy-8-iso-5-cis,-                                                                           13-trans,17-cis-prosta-                                          13-trans,17-cis-                                                                           tetraeneoic acid                                                 prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1469   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-5-cis,10,13-cis,-                                          xy-5-cis,13-cis,-                                                                          17-cis-prostatetrae-                                             17-cis-prosta-                                                                             neoic acid                                                       trienoic acid                                                                 (Example 1373)                                                         1470   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-8-iso-5-cis,10,-                                           xy-8-iso-5-cis,-                                                                           13-cis,17-cis-prostate-                                          13-cis,17-cis-                                                                             traeneoic acid                                                   prostatrienoic                                                                acid (Example                                                                 1373)                                                                  1471   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-16,16-dimethyl-                                            xy-16,16-di- 5-cis,10,13-trans-pro-                                           methyl-5-cis,13-                                                                           statrienoic acid                                                 trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1374)                                                              1472   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-16,16-dimethyl-                                            xy-16,16-di- 8-iso-5-cis,10,13-                                               methyl-8-iso-5-                                                                            trans-prostatrienoic                                             cis,13-trans-                                                                              acid                                                             prostadienoic                                                                 acid (Example                                                                 1374)                                                                  1473   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-16,16-dimethyl-                                            xy-16,16-di- 5-cis,10,13-cis-pro-                                             methyl-5-cis,13-                                                                           statrienoic acid                                                 cis-prostadie-                                                                noic acid (Exam-                                                              ple 1374)                                                              1474   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-16,16-dimethyl-                                            xy-16,16-di- 8-iso-5-cis,10,13-cis-                                           methyl-8-iso-5-                                                                            prostatrienoic acid                                              cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1374)                                                         1475   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4-nor-20-methyl-                                           xy-4-nor-20- 5-cis,10,13-trans-pro-                                           methyl-5-cis,-                                                                             statrienoic acid                                                 13-trans-prosta-                                                              dienoic acid                                                                  (Example 1375)                                                         1476   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4-nor-20-methyl-                                           xy-4-nor-20- 8-iso-5-cis,10,13-                                               methyl-8-iso-                                                                              trans-prostatrienoic                                             5-cis,13-trans-                                                                            acid                                                             prostadienoic                                                                 acid (Example                                                                 1375)                                                                  1477   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4-nor-20-methyl-                                           xy-4-nor-20- 5-cis,10,13-cis-pro-                                             methyl-5-cis,-                                                                             statrienoic acid                                                 13-cis-prostadi-                                                              enoic acid                                                                    (Example 1375)                                                         1478   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4-nor-20-methyl-                                           xy-4-nor-20- 8-iso-5-cis,10,13-                                               methyl-8-iso-                                                                              cis-prostatrienoic                                               5-cis,13-cis-                                                                              acid                                                             prostadienoic                                                                 acid (Example                                                                 1375)                                                                  1479   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a-homo-17,17-di-                                          xy-4a-homo-17,-                                                                            methyl-5-cis,10,13-                                              17-dimethyl-5-                                                                             trans-prostatrienoic                                             cis,13-trans-                                                                              acid                                                             prostadienoic                                                                 acid (Example                                                                 1376)                                                                  1480   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a-homo-17,17-di-                                          xy-4a-homo-17,-                                                                            methyl-8-iso-5-cis,10-                                           17-dimethyl-8-                                                                             13-trans-prostatrienoic                                          iso-5-cis,13-                                                                              acid                                                             trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1376)                                                              1481   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a-homo-17,17-di-                                          xy-4a-homo-17,-                                                                            methyl-5-cis,10,13-cis-                                          17-dimethyl-5-                                                                             prostatrienoic acid                                              cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1376)                                                         1482   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a-homo-17,17-di-                                          xy-4a-homo-17,-                                                                            methyl-8-iso-5-cis,10-                                           17-dimethyl-8-                                                                             13-cis-prostatrienoic                                            iso-5-cis,13-                                                                              acid                                                             cis-prostadie-                                                                noic acid (Exam-                                                              ple 1376)                                                              1483   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bis-                                                                              20-ethyl-5-cis,10,13-                                            homo-20-ethyl-                                                                             trans-prostatrienoic                                             5-cis,13-trans-                                                                            acid                                                             prostadienoic                                                                 acid (Example                                                                 1377)                                                                  1484   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bis-                                                                              20-ethyl-8-iso-5-cis,-                                           homo-20-ethyl-8-                                                                           10,13-trans-prostatrie-                                          iso-5-cis,13-                                                                              noic acid                                                        trans-prostadi-                                                               enoic acid                                                                    (Example 1377)                                                         1485   β-methyl-9-oxo-                                                                       8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bis-                                                                              20-ethyl-5-cis,10,13-                                            homo-20-ethyl-5-                                                                           cis-prostatrienoic                                               cis,13-cis-pro-                                                                            acid                                                             stadienoic acid                                                               (Example 1377)                                                         1486   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bishomo-                                                                          20-ethyl-8-iso-5-cis,-                                           20-ethyl-8-iso-                                                                            10,13-cis-prostatrie-                                            5-cis,13-cis-                                                                              noic acid                                                        prostadienoic                                                                 acid (Example                                                                 1377)                                                                  1487   8β-methyl-9-oxo                                                                       8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bishomo-                                                                          5-cis,10,13-trans,17-                                            5-cis,13-trans,-                                                                           cis-prostatetraenoic                                             17-cis-prostatri-                                                                          acid                                                             enoic acid                                                                    (Example 1378)                                                         1488   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-                                             xy-4a,4b-bishomo-                                                                          8-iso-5-cis,10,13-                                               8-iso-5-cis,13-                                                                            trans,17-cis-prostate-                                           trans,17-cis-                                                                              traenoic acid                                                    prostatrienoic                                                                acid (Example                                                                 1378)                                                                  1489   8β-methyl-9-oxo-                                                                      8β-methyl-9-oxo-15-hy-                                      11α,15-dihydro-                                                                      droxy-4a,4b-bishomo-5-                                           xy-4a,4b-bishomo-                                                                          cis,10,13-cis-17-cis-                                            5-cis,13-cis-                                                                              prostatetraenoic acid                                            17-cis-prosta-                                                                             acid                                                             trienoic acid                                                                 (Example 1378)                                                         1490   8α-methyl-9-oxo-                                                                     8α-methyl-9-oxo-15-hy-                                     11α,15-dihydro-                                                                      droxy-4a,4b-bihomo-8-                                            xy-4a,4b-bishomo-                                                                          iso-5-cis,10,13-cis-                                             8-iso-5-cis,13-                                                                            17-cis-prostatetrae-                                             cis-17-cis-pro-                                                                            noic acid                                                        statrienoic acid                                                              (Example 1378)                                                         1491   methyl 8β-methyl-                                                                     methyl 8β-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-20-methyl-                                            hydroxy-2-methyl-                                                                          10,13-trans-prostadi-                                            13-trans-proste-                                                                           enoate                                                           noate (Example                                                                1379)                                                                  1492   methyl 8α-methyl-                                                                    methyl 8α-methyl-9-oxo-                                    9-oxo-11α,15-di-                                                                     15-hydroxy-20-methyl-                                            hydroxy-20-  8-iso-10,13-trans-pro-                                           methyl-8-iso-                                                                              stadienoate                                                      13-trans-pro-                                                                 stenoate (Exam-                                                               ple 1379)                                                              1493   methyl 8β-methyl-                                                                     methyl 8β-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydrox-20-methyl-                                             hydroxy-20-  10,13-cis-prostadie-                                             methyl-13-cis-                                                                             noate                                                            prostenoate                                                                   (Example 1379)                                                         1494   methyl 8α-methyl-                                                                    methyl 8α-methyl-9-oxo-                                    9-oxo-11α,15-di-                                                                     15-hydroxy-20-methyl-                                            hydroxy-20-  8-iso-10,13-cis-pro-                                             methyl-8-iso-                                                                              stadienoate                                                      13-cis-proste-                                                                noate (Example                                                                1379)                                                                  1495   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-7a,7b-bis-                                            hydroxy-7a,7b-                                                                             homo-10,13-trans,17-                                             bishomo-13-  cis-prostatrienoate                                              trans,17-cis-                                                                 prostadienoate                                                                (Example 1380)                                                         1496   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                              9-oxo-11α,15-di-                                                               15-hydrox-7a,7b-bis-                                                          hydroxy-7a,7b-                                                                             homo-8-iso-10,13-trans-                                          bishomo-8-iso-                                                                             17-cis-prostatrienoate                                           13-trans,17-                                                                  cis-prostadie-                                                                noate (Example                                                                1380)                                                                  1497   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-                                                                        15-hydroxy-7a,7b-bis-                                            dihydroxy-7a,-                                                                             homo-10,13-cis,17-cis-                                           7b-bishomo-13-                                                                             prostatrienoate                                                  cis,17-cis-pro-                                                               stadienoate                                                                   (Example 1380)                                                         1498   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-7a,7b-bis-                                            hydroxy-7a,7b-                                                                             homo-8-iso-10,13-cis,-                                           bishomo-8-iso-                                                                             17-cis-prostatrienoate                                           13-cis,17-cis-                                                                prostadienoate                                                                (Example 1380)                                                         1499   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-2-ethyl-                                              hydroxy-2-ethyl-                                                                           16,16-dimethyl-10,13-                                            16,16-dimethyl-                                                                            trans-prostadienoate                                             13-trans-proste-                                                              noate (Example                                                                1381)                                                                  1500   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-2-ethyl-                                              hydroxy-2-ethyl-                                                                           16,16-dimethyl-8-iso-                                            16,16-dimethyl-                                                                            10,13-trans-prostadi-                                            8-iso-13-trans-                                                                            enoate                                                           prostenoate                                                                   (Example 1381)                                                         1501   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-2-ethyl-                                              hydroxy-2-ethyl-                                                                           16,16-dimethyl-10,13-                                            16,16-dimethyl-                                                                            cis-prostadienoate                                               13-cis-proste-                                                                noate (Example                                                                1381)                                                                  1502   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-2-ethyl-                                              hydroxy-2-ethyl-                                                                           16,16-dimethyl-8-iso-                                            16,16-dimethyl-                                                                            10,13-cis-prostadie-                                             8-iso-13-cis-                                                                              noate                                                            prostenoate                                                                   (Example 1381)                                                         1503   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-3,3,17,17-                                            hydroxy-3,3,17,-                                                                           tetramethyl-10,13-                                               17-tetramethyl-                                                                            trans-prostadienoate                                             13-trans-proste-                                                              noate (Example                                                                1382)                                                                  1504   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-3,3,17,17-                                            hydroxy-3,3,17,-                                                                           tetramethyl-8-iso-10,-                                           17-tetramethyl-8-                                                                          13-trans-prostadienoate                                          iso-13-trans-pro-                                                             stenoate (Example                                                             1382)                                                                  1505   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-3,3,17,17-                                            hydroxy-3,3,17,-                                                                           tetramethyl-10,13-cis-                                           17-tetramethyl-                                                                            prostadienoate                                                   13-cis-proste-                                                                noate (Example                                                                1382)                                                                  1506   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-3,3,17,17-                                            hydroxy-3,3,17,-                                                                           tetramethyl-8-iso-10,-                                           17-tetramethyl-                                                                            13-cis-prostadienoate                                            8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1382)                                                         1507   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-3-oxa-17,-                                            hydroxy-3-oxa-                                                                             17-dimethyl-10,13-trans-                                         17,17-dimethyl-                                                                            prostadienoate                                                   13-trans-proste-                                                              noate (Example                                                                1383)                                                                  1508   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-3-oxa-17,17-                                          hydroxy-3-oxa-                                                                             dimethyl-8-iso-10,13-                                            17,17-dimethyl-                                                                            trans-prostadienoate                                             8-iso-13-trans-                                                               prostenoate                                                                   (Example 1383)                                                         1509   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-3-oxa-17,17-                                          hydroxy-3-oxa-                                                                             dimethyl-10,13-cis-                                              17,17-dimethyl-                                                                            prostadienoate                                                   13-cis-proste-                                                                noate (Example                                                                1383)                                                                  1510   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-3-oxa-17,-                                            hydroxy-3-oxa-                                                                             17-dimethyl-8-iso-10,-                                           17,17-dimethyl-                                                                            13-cis-prostadienoate                                            8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1383)                                                         1511   butyl 8β-methyl-                                                                      butyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-10,13-trans-                                          hydroxy-13-trans-                                                                          prostadienoate                                                   prostenoate                                                                   (Example 1384)                                                         1512   butyl 8α-methyl-                                                                     butyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-8-iso-10,-                                            hydroxy-8-iso-13-                                                                          13-trans-prostadienoate                                          trans-prosteno-                                                               ate (Example                                                                  1384)                                                                  1513   butyl 8β-methyl-                                                                      butyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-13-cis-pro-                                           hydroxy-13-cis-                                                                            stadienoate                                                      prostenoate                                                                   (Example 1384)                                                         1514   butyl 8α-methyl-                                                                     butyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-8-iso-10,13-                                          hydroxy-8-iso-13-                                                                          cis-prostadienoate                                               cis-prostenoate                                                               (Example 1384)                                                         1515   decyl 8β-methyl-                                                                      decyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-10,13-trans,-                                         hydroxy-13-trans,-                                                                         17-cis-prostatrienoate                                           17-cis-prostadi-                                                              enoate (Example                                                               1385)                                                                  1516   decyl 8α-methyl-                                                                     decyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-8-iso-10,-                                            hydroxy-8-iso-                                                                             13-trans,17-cis-prosta-                                          13-trans,17-cis-                                                                           trienoate                                                        prostadienoate                                                                (Example 1385)                                                         1517   decyl 8β-methyl-                                                                      decyl 8β-methyl-9-oxo-                                      9-oxo-11α,15-di-                                                                     15-hydroxy-10,13-cis-                                            hydroxy-13-cis-                                                                            17-cis-prostatrienoate                                           17-cis-prostadi-                                                              enoate (Example                                                               1385)                                                                  1518   decyl 8α-methyl-                                                                     decyl 8α-methyl-9-oxo-                                     9-oxo-11α,15-di-                                                                     15-hydroxy-8-iso-10,13-                                          hydroxy-8-iso-13-                                                                          cis-17-cis-prostatrie-                                           cis-17-cis-pro-                                                                            noate                                                            stadienoate                                                                   (Example 1385)                                                         1519   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α-ace-                                                                       15-hydroxy-10,13-trans-                                          toxy-15-hydroxy-                                                                           prostadienoate                                                   13-trans-proste-                                                              noate (Example                                                                1386)                                                                  1520   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α-ace-                                                                       15-hydroxy-8-iso-10,13-                                          toxy-15-hydroxy-                                                                           trans-prostadienoate                                             8-iso-13-trans-                                                               prostenoate                                                                   (Example 1386)                                                         1521   ethyl 8β-methyl-                                                                      ethyl 8β-methyl-9-oxo-                                      9-oxo-11α-ace-                                                                       15-hydroxy-10,13-cis-                                            toxy-15-hydroxy-                                                                           prostadienoate                                                   13-cis-proste-                                                                noate (Example                                                                1386)                                                                  1522   ethyl 8α-methyl-                                                                     ethyl 8α-methyl-9-oxo-                                     9-oxo-11α-ace-                                                                       15-hydroxy-8-iso-10,13-                                          toxy-5-hydroxy-                                                                            cis-prostadienoate                                               8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1386)                                                         ______________________________________                                    

EXAMPLES 1523-1654

Treatment of the designated 9-oxo-prostenoic acid and ester derivativeslisted in Table 42 below with sodium borohydride in ethanol as describedin Example 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are separable by standard chromatographic techniques.

                  TABLE 42                                                        ______________________________________                                              Starting 8-      Product                                                      methyl-9-oxo-    8-methyl-9α/β,-                                   11α,15-di- 11α,15-trihydroxy-                               Ex-   hydroxy-13-prosten-                                                                            13-prostenoic                                          ample oic acid or ester                                                                              acid or ester                                          ______________________________________                                        1523  8β-methyl-prosta-                                                                         8β-methyl-prosta-                                       glandin E.sub.1  glandin F.sub.1 α/F.sub.1 β                       (Example 1353)                                                          1524  8α-methyl-8-iso-                                                                         8α-methyl-8-iso-pros-                                  prostaglandin E.sub.1                                                                          taglandin F.sub.1 α/F.sub.1 β                     (Example 1353)                                                          1525  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                   15-dihydroxy-13-cis-                                                                           15-trihydroxy-13-                                            prostenoic acid  cis-prostenoic acid                                          (Example 1353)                                                          1526  8α-methyl-9-oxo-                                                                         8α-methyl-9α/β,11α,-                  11α,15-dihydroxy-                                                                        15-trihydroxy-8-iso-                                         8-iso-13-cis-pros-                                                                             13-cis-prostenoic                                            tenoic acid      acid                                                         (Example 1353)                                                          1527  8β-methyl-9-oxo-                                                                          8β-methyl-9α/β,11α,-                   11α,15-dihydroxy-                                                                        15-trihydroxy-16,16-                                         16,16-dimethyl-13-                                                                             dimethyl-13-trans-                                           trans-prostenoic prostenoic acid                                              acid                                                                          (Example 1354)                                                          1528  8α-methyl-9-oxo-                                                                         8α-methyl-9α/β,11α,-                  11α,15-dihydroxy-                                                                        15-trihydroxy-16,16-                                         16,16-dimethyl-8-                                                                              dimethyl-8-iso-13-                                           iso-13-trans-pros-                                                                             trans-prostenoic acid                                        tenoic acid                                                                   (Example 1354)                                                          1529  8β-methyl-9-oxo-                                                                          8β-methyl-9α/β,11α-                    11α,15-dihydroxy-                                                                        15-trihydroxy-16,16-                                         16,16-dimethyl-13-,                                                                            dimethyl-13-cis-                                             cis-prostenoic acid                                                                            prostenoic acid                                              (Example 1354)                                                          1530  8α-methyl-9-oxo-                                                                         8α-methyl-9α/β,11α,                   11α,15-dihydroxy-                                                                        15-trihydroxy-16,16-                                         16,16-dimethyl-8-                                                                              dimethyl-8-iso-13-                                           iso-13-cis-pros- cis-prostenoic acid                                          tenoic acid                                                                   (Example 1354)                                                          1531  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                   15-dihydroxy-17,17-                                                                            15-trihydroxy-17,17-                                         dimethyl-13-trans-                                                                             dimethyl-13-trans-                                           prostenoic acid  prostenoic acid                                              (Example 1355)                                                          1532  8α-methyl-9-oxo-                                                                         8α-methyl-9α/β,11α,-                  11α,15-dihydroxy-8-                                                                      15-trihydroxy-17,17-                                         iso-17,17-di-    dimethyl-8-iso-13-                                           methyl-13-trans- trans-prostenoic                                             prostenoic acid  acid                                                         (Example 1355)                                                          1533  8β-methyl-9-oxo-                                                                          8β-methyl-9α/β,11α,-                   11α,15-dihydroxy-17,                                                                     15-trihydroxy-17,17-                                         17-dimethyl-13-cis-                                                                            dimethyl-13-cis-                                             prostenoic acid  prostenoic acid                                              (Example 1355)                                                          1534  8α-methyl-9-oxo-                                                                         8α-methyl-9α/β,11α,-                  11α,15-dihydroxy-                                                                        15-trihydroxy-8-iso-                                         17,17-dimethyl-8-                                                                              17,17-dimethyl-13-                                           iso-13-cis-pros- cis-prostenoic                                               tenoic acid      acid                                                         (Example 1355)                                                          1535  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α-                    15-dihydroxy-13- 15-trihydroxy-13-                                            trans-17-cis-pro-                                                                              trans,17-cis-pros-                                           stadienoic acid  tadienoic acid                                               (Example 1356)                                                          1536  8α-methyl-9-oxo-11α-                                                               8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-trihydroxy-8-iso-                                         13-trans,17-cis- 13-trans-17-cis-                                             prostadienoic acid                                                                             prostadienoic acid                                           (Example 1356)                                                          1537  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                   15-dihydroxy-13-cis,                                                                           15-trihydroxy-13-cis,                                        17-cis-prostadienoic                                                                           17-cis-prostadienoic                                         acid             acid                                                         (Example 1356)                                                          1538  8α-methyl-9-oxo-11α-                                                               8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-trihydroxy-8-iso-                                         13-trans-17-cis- 13-cis,17-cis-pros-                                          prostadienoic acid                                                                             tadienoic acid                                               (Example 1356)                                                          1539  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β ,11α,-                  15-dihydroxy-20- 15-trihydroxy-20-                                            ethyl-13-trans-pros-                                                                           ethyl-13-trans-pros-                                         tenoic acid      tenoic acid                                                  (Example 1357)                                                          1540  8α-methyl-9-oxo-11α-                                                               8α-methyl-9α,/β,11α,-                 15-dihydroxy-20- 15-trihydroxy-20-                                            ethyl-8-iso-13-trans-                                                                          ethyl-8-iso-13-                                              prostenoic acid  trans-prostenoic                                             (Example 1357)   acid                                                   1541  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                   15-dihydroxy-20-eth-                                                                           15-trihydroxy-20-                                            yl-13-cis-prostenoic                                                                           ethyl-13-cis-pro-                                            acid             stenoic acid                                                 (Example 1357)                                                          1542  8α-methyl-9-oxo-11α-                                                               8α-methyl-9α/β,11α,-                  15-dihydroxy-20- 15-trihydroxy-20-                                            ethyl-8-iso-13-cis-                                                                            ethyl-8-iso-13-cis-                                          prostenoic acid  prostenoic acid                                              (Example 1357)                                                          1543  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-6,7-                                                                              15-trihydroxy-6,7-                                           dinor-13-trans-pros-                                                                           dinor-13-trans-pros-                                         tenoic acid      tenoic acid                                                  (Example 1358)                                                          1544  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-6,7-                                                                              15-trihydroxy-6,7-                                           dinor-8-iso-13-trans-                                                                          dinor-8-iso-13-                                              prostenoic acid  trans-prostenoic                                             (Example 1358)   acid                                                   1545  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-6,7-                                                                              15-trihydroxy-6,7-                                           dinor-13-cis-    dinor-13-cis-                                                prostenoic acid  prostenoic acid                                              (Example 1358)                                                          1546  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-6,7-                                                                              15-trihydroxy-6,7-                                           dinor-8-iso-13-cis-                                                                            dinor-8-iso-13-cis-                                          prostenoic acid  prostenoic acid                                              (Example 1358)                                                          1547  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-5,6,7-                                                                            15-trihydroxy-5,6,7-                                         trinor-20-methyl-13-                                                                           trinor-20-methyl-13-                                         trans-prostenoic acid                                                                          trans-prostenoic acid                                        (Example 1359)                                                          1548  8α-methyl-9-oxo-11α ,-                                                             8α-methyl-9α/β,11α,-                  15-dihydroxy-5,6,7-                                                                            15-trihydroxy-5,6,7-                                         trinor-20-methyl-8-                                                                            trinor-20-methyl-8-                                          iso-13-trans-pros-                                                                             iso-13-trans-prosten-                                        tenoic acid      oic acid                                                     (Example 1359)                                                          1549  8β-methyl-9-oxo-11α-                                                                8β-methyl-9α/β,11α,-                   15-dihydroxy-5,6,7,-                                                                           15-trihydroxy-5,6,7-                                         trinor-20-methyl-                                                                              trinor-20-methyl-13-                                         13-cis-prostenoic                                                                              cis-prostenoic acid                                          acid                                                                          (Example 1359)                                                          1550  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-5,6,7-                                                                            15-trihydroxy-5,6,7-                                         trinor-20-methyl-8-                                                                            trinor-20-methyl-8-                                          iso-13-cis-prosten-                                                                            iso-13-cis-prosten-                                          oic acid         oic acid                                                     (Example 1359)                                                          1551  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-7a,7b-                                                                            15-trihydroxy-7a,7b-                                         bishomo-13-trans-                                                                              bishomo-13-trans-                                            prostenoic acid  prostenoic acid                                              (Example 1360)                                                          1552  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7a,7b-                                                                            15-trihydroxy-7a,7b-                                         bishomo-8-iso-13-                                                                              bishomo-8-iso-13-                                            trans-prostenoic trans-prostenoic                                             acid             acid                                                         (Example 1360)                                                          1553  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,                    15-dihydroxy-7a,7b-                                                                            15-trihydroxy-7a,7b-                                         bishomo-13-cis-  bishomo-13-cis-pro-                                          prostenoic acid  stenoic acid                                                 (Example 1360)                                                          1554  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7a,7b-                                                                            15-trihydroxy-7a,7b-                                         bishomo-8-iso-13-                                                                              bishomo-8-iso-13-cis-                                        cis-prostenoic acid                                                                            prostenoic acid                                              (Example 1360)                                                          1555  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-eth-                                                                            15-trihydroxy-2-                                             yl-13-trans-prosten-                                                                           ethyl-13-trans-                                              oic acid         prostenoic acid                                              (Example 1361)                                                          1556  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-2-eth-                                                                            15-trihydroxy-2-                                             yl-8-iso-13-trans-                                                                             ethyl-8-iso-13-trans-                                        prostenoic acid  prostenoic acid                                              (Example 1361)                                                          1557  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α-                    15-dihydroxy-2-ethyl-                                                                          15-trihydroxy-2-                                             13-cis-prostenoic                                                                              ethyl-13-cis-pro-                                            acid             stenoic acid                                                 (Example 1361)                                                          1558  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α-                   15-dihydroxy-2-  15-trihydroxy-2-                                             ethyl-8-iso-13-cis-                                                                            ethyl-8-iso-13-cis-                                          prostenoic acid  prostenoic acid                                              (Example 1361)                                                          1559  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3,3,20-                                                                           15-trihydroxy-3,3,20-                                        trimethyl-8-iso-13-                                                                            trimethyl-13-trans-                                          trans-prostenoic prostenoic acid                                              acid (Example 1362)                                                     1560  8α-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                   15-dihydroxy-3,3,20-                                                                           15-trihydroxy-3,3,                                           trimethyl-8-iso-13-                                                                            20-trimethyl-8-iso-                                          trans-prostenoic ac                                                                            13-trans-prostenoic                                          acid (Example 1362)                                                                            acid                                                   1561  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3,3,20-                                                                           15-trihydroxy-3,3,                                           trimethyl-13-cis-                                                                              20-trimethyl-13-cis-                                         prostenoic acid  prostenoic acid                                              (Example 1362)                                                          1562  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3,3,20-                                                                           15-trihydroxy-3,3,20-                                        trimethyl-8-iso-13-                                                                            trimethyl-8-iso-13-                                          cis-prostenoic acid                                                                            cis-prostenoic acid                                          (Example 1362)                                                          1563  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         13-trans-prostenoic                                                                            13-trans-prostenoic                                          acid             acid                                                         (Example 1363                                                           1564  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         8-iso-13-trans-  8-iso-13-trans-                                              prostenoic acid  prostenoic acid                                              (Example 1363)                                                          1565  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         8-iso-13-cis-pro-                                                                              8-iso-13-cis-pro-                                            stenoic acid     stenoic acid                                                 (Example 1363)                                                          1566  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         8-iso-13-cis-pro-                                                                              8-iso-13-cis-pro-                                            stenoic acid     stenoic acid                                                 (Example 1363)                                                          1567  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β-11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         16,16-dimethyl-13-                                                                             16,16-dimethyl-13-                                           trans-prostenoic trans-prostenoic                                             acid             acid                                                         (Example 1364)                                                          1568  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β-11α,-                  15-dihydroxy-3-oxa-                                                                            5-trihydroxy-3-oxa-                                          16,16-dimethyl-8-                                                                              16,16-dimethyl-8-                                            iso-13-trans-pro-                                                                              iso-13-trans-pro-                                            stenoic acid     stenoic acid                                                 (Example 1364)                                                          1569  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β-11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         16,16-dimethyl-13-                                                                             16,16-dimethyl-13-                                           cis-prostenoic acid                                                                            cis-prostenoic acid                                          (Example 1364)                                                          1570  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β-11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         16,16-dimethyl-8-                                                                              16,16-dimethyl-8-                                            iso-13-cis-pro-  iso-13-cis-pro-                                              stenoic acid     stenoic acid                                                 (Example 1364)                                                          1571  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         13-trans,17-cis- 13-trans,17-cis-                                             prostadienoic acid                                                                             prostadienoic acid                                           (Example 1365)                                                          1572  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         8-iso-13-trans,17-                                                                             8-iso-13-trans,17-                                           cis-prostadienoic                                                                              cis-prostadienoic                                            acid             acid                                                         (Example 1365)                                                          1573  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         13-cis,17-cis-pro-                                                                             13-cis,17-cis-                                               stadienoic acid  prostadienoic acid                                           (Example 1365)                                                          1574  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         8-iso-13-cis,17-cis-                                                                           8-iso-13-cis,17-cis-                                         prostadienoic acid                                                                             prostadienoic acid                                           (Example 1365)                                                          1575  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         20-ethyl-13-trans-                                                                             20-ethyl-13-trans-                                           prostenoic acid  prostenoic acid                                              (Example 1366)                                                          1576  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         20-ethyl-8-iso-13-                                                                             20-ethyl-8-iso-13-                                           trans-prostenoic trans-prostenoic                                             acid             acid                                                         (Example 1366)                                                          1577  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         20-ethyl-13-cis- 20-ethyl-13-cis-                                             prostenoic acid  prostenoic acid                                              (Example 1366)                                                          1578  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-3-oxa-                                                                            15-trihydroxy-3-oxa-                                         20-ethyl-8-iso-13-                                                                             20-ethyl-8-iso-13-                                           cis-prostenoic acid                                                                            cis-prostenoic acid                                          (Example 1366)                                                          1579  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-flu-                                                                            15-trihydroxy-2-                                             oro-17,17-dimethyl-                                                                            fluoro-17,17-dimeth-                                         13-trans-prostenoic                                                                            yl-13-trans-prosten-                                         acid             oic acid                                                     (Example 1367)                                                          1580  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-2-flu-                                                                            15-trihydroxy-2-                                             oro-17,17-dimethyl-                                                                            fluoro-17,17-dimeth-                                         8-iso-13-trans-  yl-8-iso-13-trans-                                           prostenoic acid  prostenoic acid                                              (Example 1367)                                                          1581  8β-methyl-9-oxo-11α,-                                                               8β-methyl 9α/β,11α,-                   15-dihydroxy-2-  15-trihydroxy-2-                                             fluoro-17,17-di- fluoro-17,17-dimeth-                                         methyl-13-cis-pros-                                                                            yl-13-cis-prostenoic                                         tenoic acid      acid                                                         (Example 1367)                                                          1582  8α-methyl-9-oxo-11α ,-                                                             8α-methyl-9α/β,11α,-                  15-dihydroxy-2-flu-                                                                            15-trihydroxy-2-                                             oro-17,17-dimethyl-                                                                            fluoro-17,17-dimeth-                                         8-iso-13-cis-pros-                                                                             yl-8-iso-13-cis-                                             tenoic acid      prostenoic acid                                              (Example 1367)                                                          1583  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-7-nor-                                                                            15-trihydroxy-7-nor-                                         13-trans-prostenoic                                                                            13-trans-prostenoic                                          acid             acid                                                         (Example 1368)                                                          1584  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7-nor-                                                                            15-trihydroxy-7-nor-                                         8-iso-13-trans-pros-                                                                           8-iso-13-trans-pros-                                         tenoic acid      tenoic acid                                                  (Example 1368)                                                          1585  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-7-nor-                                                                            15-trihydroxy-7-nor-                                         13-cis-prostenoic                                                                              13-cis-prostenoic                                            acid             acid                                                         (Example 1368)                                                          1586  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7-nor-                                                                            15-trihydroxy-7-nor-                                         8-iso-13-cis-prosten-                                                                          8-iso-13-cis-pro-                                            oic acid         stenoic acid                                                 (Example 1368)                                                          1587  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-7a-homo-                                                                          15-trihydroxy-7a-                                            16,16-dimethyl-13-                                                                             homo-16,16-dimethyl-                                         trans-prostenoic 13-trans-prostenoic                                          acid             acid                                                         (Example 1369)                                                          1588  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7a- 15-trihydroxy-7a-                                            homo-16,16-dimethyl-                                                                           homo-16,16-dimethyl-                                         8-iso-13-trans-pros-                                                                           8-iso-13-trans-pro-                                          tenoic acid      stenoic acid                                                 (Example 1369)                                                          1589  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-7a- 15-trihydroxy-7a-                                            homo-16,16-dimethyl-                                                                           homo-16,16-dimethyl-                                         13-cis-prostenoic                                                                              13-cis-prostenoic                                            acid             acid                                                         (Example 1369)                                                          1590  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-7a- 15-trihydroxy-7a-                                            homo-16,16-dimethyl-                                                                           homo-16,16-dimethyl-                                         8-iso-13-cis-prosten-                                                                          8-iso-13-cis-pros-                                           oic acid         tenoic acid                                                  (Example 1369)                                                          1591  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-phen-                                                                           15-trihydroxy-2-                                             yl-13-trans-prosten-                                                                           phenyl-13-trans-pros-                                        oic acid         tenoic acid                                                  (Example 1370)                                                          1592  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-2-phen-                                                                           15-trihydroxy-2-phen-                                        yl-8-iso-13-trans-                                                                             yl-8-iso-13-trans-                                           prostenoic acid  prostenoic acid                                              (Example 1370)                                                          1593  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-phen-                                                                           15-trihydroxy-2-phen-                                        yl-13-cis-prostenoic                                                                           yl-13-cis-prostenoic                                         acid             acid                                                         (Example 1370)                                                          1594  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-2-phen-                                                                           15-trihydroxy-2-                                             yl-8-iso-13-cis- phenyl-8-iso-13-cis-                                         prostenoic acid  prostenoic acid                                              (Example 1370)                                                          1595  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-meth-                                                                           15-trihydroxy-2-meth-                                        yl-13-trans-17-cis-                                                                            yl-13-trans,17-cis-                                          prostadienoic acid                                                                             prostadienoic acid                                           (Example 1371)                                                          1596  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α,β,11α,-                  15-dihydroxy-2-  15-trihydroxy-2-meth-                                        methyl-8-iso-13- yl-8-iso-13                                                  trans,17-cis-prosta-                                                                           cis-                                                         dienoic acid     acid                                                         (Example 1371)                                                          1597  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-2-meth-                                                                           15-trihydroxy-2-                                             yl-13-cis,17-cis-                                                                              methyl-13-cis,17-cis-                                        prostadienoic acid                                                                             prostadienoic acid                                           (Example 1371)                                                          1598  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-2-  15-trihydroxy-2-meth-                                        methyl-8-iso-13-cis,                                                                           yl-8-iso-13-cis,17-                                          17-cis-prostadienoic                                                                           cis-prostadienoic                                            acid (Example 1371)                                                                            acid                                                   1599  8β-methyl-9-oxo-11α,-                                                               8β -methyl-9α/β,11α,-                  15-dihydroxy-5,cis,-                                                                           15-trihydroxy-5 cis-                                         13-trans-prosta- 13-trans-prostadien-                                         dienoic acid     oic acid                                                     (Example 1372)                                                          1600  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-trihydroxy-8-iso-                                         5-cis-13-trans-pros-                                                                           5 cis,13-trans-pros-                                         tadienoic acid   tadienoic acid                                               (Example 1372)                                                          1601  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-5-cis,                                                                            15-trihydroxy-5 cis-                                         13-cis-prostadien-                                                                             13-cis-prostadienoic                                         oic acid         acid                                                         (Example 1372)                                                          1602  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-trihydroxy-8-iso-                                         5-cis-13-cis-prosta-                                                                           5 cis 13-cis-prosta-                                         dienoic acid     dienoic acid                                                 (Example 1372)                                                          1603  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-5-cis,-                                                                           15-trihydroxy-5-cis,-                                        13-trans,17-cis- 13-trans,17-cis-                                             prostatrienoic acid                                                           (Example 1373)                                                          1604  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-dihydroxy-8-iso-                                          5-cis,13-trans,17-                                                                             5-cis,13-trans,17-                                           cis-prostatrienoic                                                                             cis-prostatrienoic                                           acid             acid                                                         (Example 1373)                                                          1605  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-5-cis,-                                                                           15-trihydroxy-5-cis,-                                        13-cis,17-cis-prosta-                                                                          13-cis,17-cis-                                               trienoic acid    prostatrienoic acid                                          (Example 1373)                                                          1606  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-8-iso-                                                                            15-trihydroxy-8-iso-                                         5-cis,13-cis,17- 5-cis,13-cis,17-cis-                                         cis-prostatrienoic                                                                             prostatrienoic acid                                          acid                                                                          (Example 1373)                                                          1607  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-16,16-                                                                            15-trihydroxy-16,16-                                         dimethyl-5-cis,13-                                                                             dimethyl-5-cis,13-                                           trans-prostadienoic                                                                            trans-prostadienoic                                          (Example 1374)   acid                                                   1608  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-16,16-                                                                            15-trihydroxy-16,16-                                         dimethyl-8-iso-5-                                                                              dimethyl-8-iso-5-cis-                                        cis,13-trans-prosta-                                                                           13-trans-prostadien-                                         dienoic acid     oic acid                                                     (Example 1374)                                                          1609  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-16,16-                                                                            15-trihydroxy-16,16-                                         dimethyl-5-cis   dimethyl-5-cis,13-                                           13-cis-prostadienoic                                                                           cis-prostadienoic                                            acid             acid                                                         (Example 1374)                                                          1610  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-16,16-                                                                            15-trihydroxy-16,16-                                         dimethyl-8-iso-5-cis-                                                                          dimethyl-8-iso-5-cis-                                        13-cis-prostadienoic                                                                           13-cis-prostadienoic                                         acid (Example 1374)                                                                            acid                                                   1611  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4-nor-                                                                            15-trihydroxy-4-nor-                                         20-methyl-5-cis,13-                                                                            20-methyl-5-cis,13-                                          trans-prostadienoic                                                                            trans-prostadienoic                                          acid             acid                                                         (Example 1375)                                                          1612  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4-nor-                                                                            15-trihydroxy-4-nor-                                         20-methyl-8-iso-5-                                                                             20-methyl-8-iso-                                             cis,13-trans-pros-                                                                             5-cis,13-trans-                                              tadienoic acid   prostadienoic acid                                           (Example 1375)                                                          1613  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4-nor-                                                                            15-trihydroxy-4-nor-                                         20-methyl-5-cis,13-                                                                            20-methyl-5-cis,13-                                          cis-prostadienoic                                                                              cis-prostadienoic                                            acid             acid                                                         (Example 1375)                                                          1614  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4-nor-                                                                            15-trihydroxy-4-nor-                                         20-methyl-8-iso-5-                                                                             20-methyl-8-iso-5-                                           cis,13-cis-prosta-                                                                             cis,13-cis-prosta-                                           dienoic acid     dienoic acid                                                 (Example 1375)                                                          1615  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a-homo-                                                                          15-trihydroxy-4a-                                            17,17-dimethyl-5-cis-                                                                          homo-17,17-dimethyl-                                         13-trans-prostadien-                                                                           5-cis,13-trans-pros-                                         oic acid         tadienoic acid                                               (Example 1376)                                                          1616  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a-homo-                                                                          15-trihydroxy-4a-                                            17,17-dimethyl-8-                                                                              homo-17,17-dimethyl-                                         iso-5-cis,13-trans-                                                                            8-iso-5-cis,13-cis-                                          prostadienoic acid                                                                             prostadienoic acid                                           (Example 1376)                                                          1617  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a-homo-                                                                          15-trihydroxy-4a-                                            17,17-dimethyl-5-cis-                                                                          homo-17,17-dimethyl-                                         13-cis-prostadienoic                                                                           5-cis,13-cis-prosta-                                         acid             dienoic acid                                                 (Example 1376)                                                          1618  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a-homo-                                                                          15-trihydroxy-4a-                                            17,17-dimethyl-8-iso-                                                                          homo-17,17-dimethyl-                                         5-cis,13-cis-prosta-                                                                           8-iso-5-cis,13-cis-                                          dienoic acid     prostadienoic acid                                           (Example 1376)                                                          1619  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bishomo-20-ethyl-5-                                                                            bishomo-20-ethyl-                                            cis,13-trans-prosta-                                                                           5-cis,13-trans-pros-                                         dienoic acid     tadienoic acid                                               (Example 1377)                                                          1620  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bishomo-20-ethyl-8-                                                                            bishomo-20-ethyl-8-                                          iso-5-cis,13-trans-                                                                            iso-5-cis,13-trans-                                          prostadienoic acid                                                                             prostadienoic acid                                           (Example 1377)                                                          1621  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bishomo-20-ethyl-5-                                                                            bishomo-20-ethyl-5-                                          cis,13-cis-prosta-                                                                             cis,13-cis-prosta-                                           dienoic acid     dienoic acid                                                 (Example 1377)                                                          1622  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bishomo-20-ethyl-8-                                                                            bishomo-20-ethyl-8-                                          iso-5-cis,13-cis-                                                                              iso-5-cis,13-cis-                                            prostadienoic acid                                                                             prostadienoic                                                (Example 1377)                                                          1623  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bis-homo-5-cis,13-                                                                             bishomo-5-cis,13-                                            trans,17-cis-prosta-                                                                           trans,17-cis-prosta-                                         trienoic acid    trienoic acid                                                (Example 1378)                                                          1624  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bis-homo-8-iso-5-cis-                                                                          bis-homo-8-iso-5-cis,-                                       13-trans,17-cis-pros-                                                                          13-trans,17-cis-                                             tatrienoic acid  prostatrienoic acid                                          (Example 1378)                                                          1625  8β-methyl-9-oxo-11α,-                                                               8β-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bis-homo-5-cis,13-                                                                             bis-homo-5-cis,13-                                           cis,17-cis-pros- cis-17-cis-prosta-                                           tatrienoic acid  trienoic acid                                                (Example 1378)                                                          1626  8α-methyl-9-oxo-11α,-                                                              8α-methyl-9α/β,11α,-                  15-dihydroxy-4a,4b-                                                                            15-trihydroxy-4a,4b-                                         bis-homo-8-iso-5-cis,                                                                          bis-homo-8-iso-5-                                            13-cis-17-cis-pros-                                                                            cis,13-cis,17-cis-                                           tatrienoic acid  prostatrienoic acid                                          (Example 1378)                                                          1627  methyl 8β-methyl-9-                                                                       methyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            20-methyl-13-trans-                                                                            hydroxy-20-methyl-                                           prostenoate      13-trans-prostenoate                                         (Example 1379)                                                          1628  methyl 8α-methyl-9-                                                                      methyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            20-methyl-8-iso-13-                                                                            hydroxy-20-methyl-                                           trans-prostenoate                                                                              8-iso-13-trans-pros-                                         (Example 1379)   tenoate                                                1629  methyl 8β-methyl-9-                                                                       methyl 8β-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            20-methyl-13-cis-                                                                              hydroxy-20-methyl-                                           prostenoate      13-cis-prostenoate                                           (Example 1379)                                                          1630  methyl 8α-methyl-9-                                                                      methyl 8α-methyl-                                      oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            20-methyl-8-iso-13-                                                                            hydroxy-20-methyl-                                           cis-prostenoate  8-iso-13-cis-pros-                                           (Example 1379)   tenoate                                                1631  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            7a,7b-bis-homo-13-                                                                             hydroxy-7a,7b-bis-                                           trans,17-cis-prosta-                                                                           homo-13-trans,17-                                            dienoate         cis-prostadienoate                                           (Example 1380)                                                          1632  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-9α/-                             oxo-11α,15-dihydroxy-                                                                    β,11α,15-trihydroxy-                              7a,7b-bis-homo-8-iso-                                                                          7a,7b-bis-homo-8-                                            13-trans,17-cis- iso-13-trans,17-cis-                                         prostadienoate   prostadienoate                                               (Example 1380)                                                          1633  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            7a,7b-bis-homo-13-                                                                             hydroxy-7a,7b-bis-                                           cis-17-cis-prosta-                                                                             homo-13-cis,17-cis-                                          dienoate         prostadienoate                                               (Example 1380)                                                          1634  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            7a,7b-bis-homo-8-                                                                              hydroxy-7a,7b-bis-                                           iso-13-cis,17-cis-                                                                             homo-8-iso-13-cis-                                           prostadienoate   17-cis-prosta-                                               (Example 1380)   dienoate                                               1635  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            2-ethyl-16,16-dimeth-                                                                          hydroxy-2-ethyl-16,                                          yl-13-trans-prosten-                                                                           16-dimethyl-13-                                              oate             trans-prostenoate                                            (Example 1381)                                                          1636  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            2-ethyl-16,16-di-                                                                              hydroxy-2-ethyl-                                             methyl-8-iso-13- 16,16-dimethyl-8-                                            trans-prostenoate                                                                              iso-13-trans-pros-                                           (Example 1381)   tenoate                                                1637  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            2-ethyl-16,16-di-                                                                              hydroxy-2-ethyl-                                             methyl-13-cis-pros-                                                                            16,16-dimethyl-13-                                           tenoate          cis-prostenoate                                              (Example 1381)                                                          1638  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            2-ethyl-16,16-di-                                                                              hydroxy-2-ethyl-16,-                                         methyl-8-iso-13-cis-                                                                           16-dimethyl-8-iso-                                           prostenoate      13-cis-prostenoate                                           (Example 1381)                                                          1639  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α /β,11α,15-tri-                           3,3,17,17-tetra- hydroxy-3,3,17,17-                                           methyl-13-trans- tetramethyl-13-                                              prostenoate      trans-prostenoate                                            (Example 1382)                                                          1640  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,15-tri-                                      3,3,17,17-tetra- hydroxy-3,3,17,17-                                           methyl-8-iso-13- tetramethyl-8-iso-                                           trans-prostenoate                                                                              13-trans-prosten-                                            (Example 1382)   oate                                                   1641  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3,3,17,17-tetramethyl-                                                                         hydroxy-3,3,17,17-                                           13-cis-prostenoate                                                                             tetramethyl-13-cis-                                          (Example 1382)   prostenoate                                            1642  ethyl-8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3,3,17,17-tetramethyl-                                                                         hydroxy-3,3,17,17-                                           8-iso-13-cis-prosten-                                                                          tetramethyl-8-iso-                                           oate             13-cis-prostenoate                                           (Example 1382)                                                          1643  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3-oxa-17,17-dimethyl-                                                                          hydroxy-3-oxa-17,17-                                         13-trans-prostenoate                                                                           dimethyl-13-trans-                                           (Example 1383)   prostenoate                                            1644  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3-oxa-17,17-dimethyl-                                                                          hydroxy-3-oxa-17,17-                                         8-iso-13-trans-pros-                                                                           dimethyl-8-iso-13-                                           tenoate          trans-prostenoate                                            (Example 1383)                                                          1645  ethyl 8β-methyl-9-                                                                        ethyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3-oxa-17,17-dimethyl-                                                                          hydroxy-3-oxa-17,17-                                         13-cis-prostenoate                                                                             dimethyl-13-cis-                                             (Example 1383)   prostenoate                                            1646  ethyl 8α-methyl-9-                                                                       ethyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            3-oxa-17,17-dimethyl-                                                                          hydroxy-3-oxa-17,17-                                         8-iso-13-cis-pros-                                                                             dimethyl-8-iso-13-                                           tenoate          cis-prostenoate                                              (Example 1383)                                                          1647  butyl 8β-methyl-9-                                                                        butyl 8β-methyl-                                        oxo-11α,15-hydroxy-                                                                      9α /β,11α,15-tri-                           13-trans-prostenoate                                                                           hydroxy-13-trans-                                            (Example 1384)   prostenoate                                            1648  butyl 8α-methyl-9-                                                                       butyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,15-tri-                                      8-iso-13-trans-  hydroxy-8-iso-13-                                            prostenoate      trans-prostenoate                                            (Example 1384)                                                          1649  butyl 8β-methyl-9-                                                                        butyl 8β-methyl-                                        oxo-11α,15-dihydroxy                                                                     9α/β,11α,15-tri-                            13-cis-prostenoate                                                                             hydroxy-13-cis-                                              (Example 1384)   prostenoate                                            1650  butyl 8α-methyl-9-                                                                       butyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            8-iso-13-cis-pros-                                                                             hydroxy-8-iso-13-                                            tenoate          cis-prostenoate                                              (Example 1384)                                                          1651  decyl 8β-methyl-9-                                                                        decyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            13-trans,17-cis- hydroxy-13-trans,-                                           prostadienoate   17-cis-prosta-                                               (Example 1385)   dienoate                                               1652  decyl 8α-methyl-9-                                                                       decyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            8-iso-13-trans,17-                                                                             hydroxy-8-iso-13-                                            cis-prostadienoate                                                                             trans,17-cis-pro-                                            (Example 1385)   stadienoate                                            1653  decyl 8β-methyl-9-                                                                        decyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            13-cis,17-cis-pros-                                                                            hydroxy-13-cis,17-                                           tadienoate       cis-prostadienoate                                           (Example 1385)                                                          1654  decyl 8α-methyl-9-                                                                       decyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                    9α/β,11α,15-tri-                            8-iso-13-cis,17-cis-                                                                           hydroxy-8-iso-13-                                            prostadienoate   cis,17-cis-prosta-                                           (Example 1385)   dienoate                                               ______________________________________                                    

EXAMPLES 1655-1781

Saponification of the alkyl esters designated in Table 43 below by theprocedure described in Example 495 is productive of the carboxylic acidsof the table. The epimeric 9α and 9β hydroxy products are separable bythe usual chromatographic procedures.

                  TABLE 43                                                        ______________________________________                                        Ex-   Starting alkyl                                                          ample prostenoate     Product prostenoic acid                                 ______________________________________                                        1655  11-deoxy-8β-meth-                                                                        11-deoxy-8β-methyl-pros-                                 yl-prostaglandin                                                                              taglandin E.sub.1                                             E.sub.1 methyl ester                                                          (Example 1188)                                                          1656  11-deoxy-8α-meth-                                                                       11-deoxy-8α-methyl-8-                                   yl-8-iso-prosta-                                                                              iso-prostaglandin E.sub.1                                     glandin E.sub.1 meth-                                                         yl ester (Exam-                                                               ple 1188)                                                               1657  methyl 15-hy-   15-hydroxy-8β-methyl-9-                                  droxy-8β-methyl                                                                          oxo-13-cis-prostenoic                                         9-oxo-13-cis    acid                                                          prostenoate                                                                   (Example 1188)                                                          1658  methyl-15-hy-   15-hydroxy-8αmethyl-8-                                  droxy-8α-methyl-                                                                        iso-9-oxo-13-cis-                                             8-iso-9-oxo-13- prostenoic acid                                               cis-prostenoate                                                               (Example 1188)                                                          1659  11-deoxy-8β-meth-                                                                        11-deoxy-8β-methyl-                                      yl-prostaglandin                                                                              prostaglandin F.sub.1 α/β                          F.sub.1 α/β methyl                                                 esters (Ex. 1206)                                                       1660  11-deoxy-8α-meth-                                                                       11-deoxy-8α-methyl-8-                                   yl-8-iso-prosta-                                                                              iso-prostaglandin                                             glandin F.sub.1 α/β                                                                F.sub.1 α/β                                        methyl esters                                                                 (Example 1207)                                                          1661  methyl 9α,15-di-                                                                        9α,15-dihydroxy-8β-meth-                           hydroxy-8β-meth-                                                                         yl-13-cis-prostenoic                                          yl-13-cis-pros- acid                                                          tenoate (Example                                                              1208)                                                                   1662  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-16,16-dimethyl-13-                                      droxy-16,16-di- trans-prostenoic acid                                         methyl-13-trans-                                                              prostenoate                                                                   (Example 1190)                                                          1663  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-16,16-dimethyl-8-                                       droxy-16,16-di- iso-13-trans-prosten-                                         methyl-8-iso-13-                                                                              oic acid                                                      trans-prosteno-                                                               ate (Example                                                                  1190)                                                                   1664  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-16,16-dimethyl-                                         droxy-16,16-di- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1190)                                                          1665  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-16,16-dimethyl-                                         droxy-16,16-di- 8-iso-13-cis-prosten-                                         methyl-8-iso-13-                                                                              oic acid                                                      cis-prostenoate                                                               (Example 1190)                                                          1666  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 13-trans-prostenoic                                           methyl-13-trans-                                                                              acid                                                          prostenoate                                                                   (Example 1191)                                                          1667  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 8-iso-13-trans-pros-                                          methyl-8-iso-13-                                                                              tenoic acid                                                   trans-prosteno-                                                               ate (Example                                                                  1191)                                                                   1668  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-17,17-dimethyl-                                         droxy-17,17-di- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1191)                                                          1669  ethyl 8α-methyl-                                                                        8αmethyl-9-oxo-15-hy-                                   9-oxo-5-hy-     droxy-17,17-dimethyl-8-                                       droxy-17,17-di- iso-13-cis-prostenoic                                         methyl-8-iso-13-                                                                              acid                                                          cis-prostenoate                                                               (Example 1191)                                                          1670  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-13-trans,17-cis-                                        droxy-13-trans,-                                                                              prostadienoic acid                                            17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                   1671  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-13-trans,17-                                      droxy-8-iso-13- cis-prostadienoic acid                                        trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                          1672  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-13-cis,17-cis-                                          droxy-13-cis,17-                                                                              prostadienoic acid                                            cis-prostadien-                                                               oate (Example                                                                 1192)                                                                   1673  ethyl 8αmethyl-                                                                         8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-13-cis,17-                                        droxy-8-iso-13- cis-prostadienoic acid                                        cis,17-cis-pros-                                                              tadienoate (Ex-                                                               ample 1192)                                                             1674  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-13-trans-                                      droxy-20-ethyl- prostenoic acid                                               13-trans-pros-                                                                tenoate (Example                                                              1193)                                                                   1675  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-13-                                      droxy-20-ethyl- trans-prostenoic acid                                         8-iso-13-trans-                                                               prostenoate                                                                   (Example 1193)                                                          1676  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-13-cis-                                        droxy-20-ethyl- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1193)                                                                   1677  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-13-                                      droxy-20-ethyl- cis-prostenoic acid                                           8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                          1678  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7a,7b-bishomo-13-                                       droxy-7a,7b-bis-                                                                              trans-prostenoic acid                                         homo-13-trans-                                                                prostenoate                                                                   (Example 1195)                                                          1679  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7a,7b-bishomo-8-                                        droxy-7a,7b-bis-                                                                              iso-13-trans-prostenoic                                       homo-8-iso-13-  acid                                                          trans-prosteno-                                                               ate (Example                                                                  1195)                                                                   1680  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7a,7b-bishomo-13-                                       droxy-7a,7b-bis-                                                                              cis-prostenoic acid                                           homo-13-cis-                                                                  prostenoate                                                                   (Example 1195)                                                          1681  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7a,7b-bishomo-8-                                        droxy-7a,7b-bis-                                                                              iso-13-cis-prostenoic                                         homo-8-iso-13-  acid                                                          cis-prostenoate                                                               (Example 1195)                                                          1682  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2,20-bisethyl-13-                                       droxy-2,20-bis- trans-prostenoic acid                                         ethyl-13-trans-                                                               prostenoate                                                                   (Example 1196)                                                          1683  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2,20-bisethyl-8-                                        droxy-2,20-bis- iso-13-trans-prostenoic                                       ethyl-8-iso-13- acid                                                          trans-prosten-                                                                oate (Example                                                                 1196)                                                                   1684  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2,20-bisethyl-13-                                       droxy-2,20-bis- cis-prostenoic acid                                           ethyl-13-cis-                                                                 prostenoate                                                                   (Example 1196)                                                          1685  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2,20-bisethyl-8-                                        droxy-2,20-bis- iso-13-cis-prostenoic                                         ethyl-8-iso-13- acid                                                          cis-prostenoate                                                               (Example 1196)                                                          1686  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-13-trans-pros-                                         16-dimethyl-13- tenoic acid                                                   trans-prosteno-                                                               ate (Example                                                                  1197)                                                                   1687  ethyl 8α-methyl-                                                                        8αmethyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-8-iso-13-trans-                                        16-dimethyl-8-  prostenoic acid                                               iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                          1688  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-13-cis-prostenoic                                      16-dimethyl-13- acid                                                          cis-prostenoate                                                               (Example 1197)                                                          1689  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-16,16-di-                                         droxy-3-oxa-16,-                                                                              methyl-8-iso-13-cis-                                          16-dimethyl-8-iso-                                                                            prostenoic acid                                               13-cis-prosteno-                                                              ate (Example 1197)                                                      1690  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-13-trans,-                                        droxy-3-oxa-13- 17-cis-prostadienoic                                          trans,17-cis-   acid                                                          prostadienoate                                                                (Example 1198)                                                          1691  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-8-iso-13-                                         droxy-3-oxa-8-  trans,17-cis-prostadi-                                        iso-13-trans,17-                                                                              enoic acid                                                    cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                   1692  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-3-oxa-13-cis,17-                                        droxy-3-oxa-13- cis-prostadienoic acid                                        cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                               1693  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-3-oxa-8-iso-13-                                         droxy-3-oxa-8-  cis,17-cis-prostadi-                                          iso-13-cis,17-  enoic acid                                                    cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                   1694  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 13-trans-prostenoic                                           methyl-13-trans-                                                                              acid                                                          prostenoate                                                                   (Example 1199)                                                          1695  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 8-iso-13-trans-pros-                                          methyl-8-iso-   tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1199)                                                                   1696  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 13-cis-prostenoic acid                                        methyl-13-cis-                                                                prostenoate                                                                   (Example 1199)                                                          1697  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-7-nor-20-methyl-                                        droxy-7-nor-20- 8-iso-13-cis-prosteno-                                        methyl-8-iso-   ic acid                                                       13-cis-prosten-                                                               oate (Example                                                                 1199)                                                                   1698  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-fluoro-17,17-di-                                      droxy-2-fluoro- methyl-13-trans-pros-                                         17,17-dimethyl- tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1200)                                                                   1699  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-8-iso-13-                                            17,17-dimethyl- trans-prostenoic acid                                         8-iso-13-trans-                                                               prostenoate                                                                   (Example 1200)                                                          1700  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-13-cis-                                              17,17-dimethyl- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1200)                                                                   1701  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-fluoro-17,17-                                         droxy-2-fluoro- dimethyl-8-iso-13-cis-                                        17,17-dimethyl- prostenoic acid                                               8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                          1702  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-10a-homo-13-                                            droxy-10a-homo- trans-prostenoic acid                                         13-trans-pros-                                                                tenoate (Example                                                              1201)                                                                   1703  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-10a-homo-8-iso-                                         droxy-10a-homo-8-                                                                             13-trans-prostenoic                                           iso-13-trans-   acid                                                          prostenoate                                                                   (Example 1201)                                                          1704  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-10a-homo-13-cis-                                        droxy-10a-homo- prostenoic acid                                               13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                   1705  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-10a-homo-8-iso-                                         droxy-10a-homo- 13-cis-prostenoic acid                                        8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1201)                                                          1706  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-phenyl-2-meth-                                        droxy-2-phenyl- yl-13-trans-prostenoic                                        20-methyl-13-   acid                                                          trans-prosteno-                                                               ate (Example                                                                  1202)                                                                   1707  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-8-iso-13-trans-pros-                                       20-methyl-8-iso-                                                                              tenoic acid                                                   13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                   1708  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-13-cis-prostenoic                                          20-methyl-13-   acid                                                          cis-prostenoate                                                               (Example 1202)                                                          1709  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-2-phenyl-20-meth-                                       droxy-2-phenyl- yl-8-iso-13-cis-prosten-                                      20-methyl-8-iso-                                                                              oic acid                                                      13-cis-prosten-                                                               oate (Example                                                                 1202)                                                                   1710  methyl 8β-methyl-                                                                        8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-trans,17-                                      droxy-5-cis,13- cis-prostatrienoic acid                                       trans,17-cis-                                                                 prostatrienoate                                                               (Example 1203)                                                          1711  methyl 8α-methyl-                                                                       8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  trans,17-cis-prostatri-                                       cis,13-trans,17-                                                                              enoic acid                                                    cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                   1712  methyl 8β-methyl-                                                                        8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-cis,17-                                        droxy-5-cis,13- cis-prostatrienoic acid                                       cis,17-cis-pros-                                                              tatrienoate                                                                   (Example 1203)                                                          1713  methyl 8α-methyl-                                                                       8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  cis,17-cis-prostatri-                                         cis,13-cis,17-  enoic acid                                                    cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                   1714  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-trans-                                         droxy-5-cis,13- prostadienoic acid                                            trans-prostadi-                                                               enoate (Example                                                               1204)                                                                   1715  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  trans-prostadienoic                                           cis,13-trans-   acid                                                          prostadienoate                                                                (Example 1204)                                                          1716  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-5-cis,13-cis-                                           droxy-5-cis,13- prostadienoic acid                                            cis-prostadieno-                                                              ate (Example                                                                  1204)                                                                   1717  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-8-iso-5-cis,13-                                         droxy-8-iso-5-  cis-prostadienoic acid                                        cis,13-cis-pros-                                                              tadienoate (Exam-                                                             ple 1204)                                                               1718  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-5-cis,13-                                      droxy-20-ethyl- trans-prostadienoic acid                                      5-cis,13-trans-                                                               prostadienoate                                                                (Example 1205)                                                          1719  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-5-                                       droxy-20-ethyl- cis,13-trans-prostadi-                                        8-iso-5-cis,13- enoic acid                                                    trans-prostadi-                                                               enoate (Example                                                               1205)                                                                   1720  ethyl 8β-methyl-                                                                         8β-methyl-9-oxo-15-hy-                                   9-oxo-15-hy-    droxy-20-ethyl-5-cis,13-                                      droxy-20-ethyl- cis-prostadienoic acid                                        5-cis,13-cis-                                                                 prostadienoate                                                                (Example 1205)                                                          1721  ethyl 8α-methyl-                                                                        8α-methyl-9-oxo-15-hy-                                  9-oxo-15-hy-    droxy-20-ethyl-8-iso-                                         droxy-20-ethyl- 5-cis,13-cis-prosta-                                          8-iso-5-cis,13- dienoic acid                                                  cis-prostadien-                                                               oate (Example                                                                 1205)                                                                   ______________________________________                                        Ex-   Starting alkyl                                                          ample ester of Example                                                                              Product prostenoic acid                                 ______________________________________                                        1722  1210            8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      trans-prostenoic acid                                   1723  1211            8α-methyl-9α/β,15-di-                                        hydroxy-16,16-dimethyl-                                                       8-iso-13-trans-pros-                                                          tenoic acid                                             1724  1212            8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      cis-prostenoic acid                                     1725  1213            8α-methyl-9α/β,15-dihy-                                      hydroxy-16,16-dimethyl-                                                       8-iso-13-cis-prostenoic                                                       acid                                                    1726  1214            8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-                                                         13-trans-prostenoic                                                           acid                                                    1727  1215            8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-trans-prosten-                                                         oic acid                                                1728  1216            8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-13-                                                      cis-prostenoic acid                                     1729  1217            8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-cis-prostenoic                                                         acid                                                    1730  1218            8β-methyl-9α/β,15-dihy-                                       droxy-13-trans,17-cis-                                                        prostadienoic acid                                      1731  1219            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-13-trans,17-                                                      cis-prostadienoic acid                                  1732  1220            8β-methyl-9α/β,15-dihy-                                       droxy-13-cis,17-cis-                                                          prostadienoic acid                                      1733  1221            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-13-cis,17-                                                        cis-prostadienoic acid                                  1734  1222            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-trans-                                                      prostenoic acid                                         1735  1223            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         13-trans-prostenoic                                                           acid                                                    1736  1224            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-cis-                                                        prostenoic acid                                         1737  1225            8α-methyl-9α/β ,15-dihy-                                     droxy-20-ethyl-8-iso-                                                         13-cis-prostenoic acid                                  1738  1230            8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       trans-prostenoic acid                                   1739  1231            8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-bishomo-8-                                                        iso-13-trans-prosten-                                                         oic acid                                                1740  1232            8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       cis-prostenoic acid                                     1741  1233            8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-bishomo-8-                                                        iso-13-cis-prostenoic                                                         acid                                                    1742  1234            8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       trans-prostenoic acid                                   1743  1235            8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-trans-prosten-                                                         oic acid                                                1744  1236            8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       cis-prostenoic acid                                     1745  1237            8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-cis-prostenoic                                                         acid                                                    1746  1238            8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-13-trans-pros-                                                         tenoic acid                                             1747  1239            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-trans-                                                        prostenoic acid                                         1748  1240            8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-13-cis-prosten-                                                        oic acid                                                1749  1241            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-cis-                                                          prostenoic acid                                         1750  1242            8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-13-trans,17-                                                      cis-prostadienoic acid                                  1751  1243            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         trans,17-cis-prostadi-                                                        enoic acid                                              1752  1244            8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-13-cis,17-                                                        cis-prostadienoic acid                                  1753  1245            8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         cis,17-cis-prostadien-                                                        oic acid                                                1754  1246            8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-trans-prostenoic                                                           acid                                                    1755  1247            8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-trans-pros-                                                          tenoic acid                                             1756  1248            8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-cis-prostenoic acid                                  1757  1249            8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-cis-prosteno-                                                        ic acid                                                 1758  1250            8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-trans-                                                            prostenoic acid                                         1759  1251            8α-methyl-9α/β,15-dihy-                                      droxy-2-fluoro-17,17-                                                         dimethyl-8-iso-13-                                                            trans-prostenoic acid                                   1760  1252            8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-cis-pros-                                                         tenoic acid                                             1761  1253            8α-methyl-9α/β,15-dihy-                                      droxy-2-fluoro-17,17-                                                         dimethyl-8-iso-13-cis-                                                        prostenoic acid                                         1762  1254            8β-methyl-9α/β,15-dihy-                                       droxy-10a-homo-13-trans-                                                      prostenoic acid                                         1763  1255            8α-methyl-9α/β,15-dihy-                                      droxy-10a-homo-8-iso-                                                         13-trans-prostenoic                                                           acid                                                    1764  1256            8β-methyl-9α/β,15-dihy-                                       droxy-10a-homo-13-cis-                                                        prostenoic acid                                         1765  1257            8α-methyl-9α/β,15-dihy-                                      droxy-10a-homo-8-iso-                                                         13-cis-prostenoic acid                                  1766  1258            8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-trans-prostenoic                                                        acid                                                    1767  1259            8α-methyl-9α/β,15-dihy-                                      droxy-2-phenyl-20-meth-                                                       yl-8-iso-13-trans-pros-                                                       tenoic acid                                             1768  1260            8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-cis-prostenoic                                                          acid                                                    1769  1261            8α-methyl-9α/β,15-dihy-                                      droxy-2-phenyl-20-meth-                                                       yl-8-iso-13-cis-prosten-                                                      oic acid                                                1770  1262            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-trans,17-                                                      cis-prostatrienoic acid                                 1771  1263            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans,17-cis-prostatri-                                                       enoic acid                                              1772  1264            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis,17-                                                        cis-prostatrienoic acid                                 1773  1265            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis,17-cis-prostatri-                                                         enoic acid                                              1774  1266            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-trans-                                                         prostadienoic acid                                      1775  1267            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans-prostadienoic                                                           acid                                                    1776  1268            8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis-                                                           prostadienoic acid                                      1777  1269            8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis-prostadienoic acid                                  1778  1270            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-5-cis,13-                                                      trans-prostadienoic                                                           acid                                                    1779  1271            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         5-cis,13-trans-pros-                                                          tadienoic acid                                          1780  1272            8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-5-cis,-                                                        13-cis-prostadienoic                                                          acid                                                    1781  1273            8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         5-cis,13-cis-prosta-                                                          dienoic acid                                            ______________________________________                                    

EXAMPLES 1782-1815

Catalytic hydrogenation of the 13-trans-prostenoic acids or esterslisted below in Table 44 by the procedure described in Example 699furnishes the product prostanoic acids of the table.

                  TABLE 44                                                        ______________________________________                                                Starting 13- Products                                                 Ex-     trans-prostenoic                                                                           8-methylprostanoic                                       ample   acid or ester of                                                                           acids or esters                                                  Example                                                               ______________________________________                                        1782    1206         Methyl 8β-methyl-9α/β,                                        15-dihydroxy-                                                                 prostanoate                                              1783    1207         Methyl 8α-methyl-9α/β,                                       15-dihydroxy-8-iso-                                                           prostanoate                                              1784    1210         Ethyl 8β-methyl-9α/β,                                         15-dihydroxy-16,16-                                                           dimethyl-prostanoate                                     1785    1226         Decyl 8β-methyl-9α/β,                                         15-dihydroxy-20-methyl-                                                       prostanoate                                              1786    1655         8β-methyl-9-oxo-15-di-                                                   hydroxy-prostanoic acid                                  1787    1656         8α-methyl-9-oxo-15-di-                                                  hydroxy-8-iso-prostan-                                                        oic acid                                                 1788    1659         8β-methyl-9α/β,15-di-                                         hydroxy-prostanoic acid                                  1789    1660         8α-methyl-9α/β,15-di-                                        hydroxy-8-iso-prostan-                                                        oic acid                                                 1790    1678         8β-methyl-9-oxo-15-hy-                                                   droxy-7a,7b-bishomo-                                                          prostanoic acid                                          1791    1683         8α-methyl-9-oxo-15-                                                     hydroxy-2,20-bisethyl-                                                        8-iso-prostanoic acid                                    1792    1686         8β-methyl-9-oxo-15-                                                      hydroxy-3-oxa-16,16-                                                          dimethyl-prostanoic                                                           acid                                                     1793    1694         8β-methyl-9-oxo-15-                                                      hydroxy-7-nor-20-                                                             methyl-prostanoic acid                                   1794    1702         8β-methyl-9-oxo-15-                                                      hydroxy-10a-homo-                                                             prostanoic acid                                          1795    1523         8β-methyl-9α/β,11α,15-                                  trihydroxy-prostanoic                                                         acid                                                     1796    1524         8α-methyl-9α/β,11α,15-                                 trihydroxy-8-iso-                                                             prostanoic acid                                          1797    1527         8β-methyl-9α/β,11α,15-                                  trihydroxy-16,16-di-                                                          methyl-prostanoic acid                                   1798    1531         8β-methyl-9α/β,11α,15-                                  trihydroxy-17,17-di-                                                          methyl-prostanoic acid                                   1799    1539         8β-methyl-9α/β-11α,15-                                  trihydroxy-20-ethyl-                                                          prostanoic acid                                          1800    1552         8α-methyl-9α/β,11α,15-                                 trihydroxy-7a,7b-bis-                                                         homo-8-iso-prostanoic                                                         acid                                                     1801    1551         8β-methyl-9α/β,11α,15-                                  trihydroxy-7a,7b-bis-                                                         homo-prostanoic acid                                     1802    1555         8β-methyl-9α/β,11α,15-                                  trihydroxy-2-ethyl-                                                           prostanoic acid                                          1803    1559         8β-methyl-9α/β,11α,15-                                  trihydroxy-3,3,20-tri-                                                        methyl-prostanoic acid                                   1804    1563         8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-                                                             prostanoic acid                                          1805    1567         8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-16,                                                          16-dimethyl-prostanoic                                                        acid                                                     1806    1587         8β-methyl-9α/β,11α,15-                                  trihydroxy-7a-homo-                                                           16,16-dimethyl-pro-                                                           stanoic acid                                             1807    1643         Ethyl 8β-methyl-9α/β,                                         11α,15 trihydroxy-3-                                                    oxa-17,17-dimethyl-                                                           prostanoic acid                                          1808    1816         8β,15-dimethyl-9α/β,15-                                       dihydroxy-prostanoic                                                          acid                                                     1809    1817         8β,15-dimethyl-9-oxo-                                                    15-hydroxy-prostanoic                                                         acid                                                     1810    1819         8α,15-dimethyl-9-oxo-                                                   15-dihydroxy-8-iso-                                                           prostanoic acid                                          1811    1834         8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-                                                      prostanoic acid                                          1812    1835         8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-                                                       prostanoic acid                                          1813    1837         8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-8-                                                     iso-prostanoic acid                                      1814    1843         8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-7a,                                                    7b-bishomo-prostanoic                                                         acid                                                     1815    1849         8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-prostanoic acid                                      ______________________________________                                    

EXAMPLES 1816-1859

Treatment by the procedure described in Example 1082 of the8-methyl-9α/β,15-dihydroxy-prostenoic acids listed in Table 45 belowsuccessively with 2,3-dichloro-5,6-dicyanobenzoquinone to give thecorresponding 15 -keto derivatives; 2.4 equivalents each oftriethylamine and trimethylsilyl chloride to give the corresponding9α/β-O-trimethylsilyl ether trimethylsilyl prostenoate ester in theinstance of the 11α-hydroxy derivatives an additional 1.1 equivalenteach of triethylamine and trimethylsilyl chloride is used and the11α-O-trimethylsilyl ether derivative is obtained); methyl magnesiumbromide to give the 15 -methyl-15-hydroxy bis or tris trimethylsilylblocked ether-ester; methanol-water-acetic acid for deblocking of thetrimethylsilyl ether and ester blocking groups to give the listed9α/β-hydroxy-15-methyl-15-hydroxy derivatives. In the 11-deoxy seriestreatment of these 9α/β-hydroxy-15-methyl-15-hydroxy products withCollins reagent in methylene chloride provides the corresponding11-deoxy-9-oxo-15-hydroxy-15-methyl-prostenoic acids, also listed in thetable. In the 11α-hydroxy series, treatment of the 9α/β,11α-15-trihydroxy-15-methyl derivatives with 1.1 molar equivalents eachof triethylamine and trimethylsilyl chloride provides the corresponding11α-O-trimethylsilyloxy-9α/β,15-dihydroxy derivative, which on oxidationin the usual way with Collins reagent in methylene chloride followed bysilyl ether cleavage (treatment with methanol-water-acetic acid by theprocedure described in Example 1082) provides the corresponding9-oxo-11α,15-dihydroxy-15-methyl-prostenoic acids of the Table.

                  TABLE 45                                                        ______________________________________                                        Ex-   Starting 9α/β, (or                                           ample 9α),15-dihydroxy-                                                                       Product                                                       or 9α/β (or 9α),                                                             8,15-dimethyl-15-hy-                                          11α,15-trihydroxy                                                                       droxy-prostanoic                                              derivative of   acids                                                         Example                                                                 ______________________________________                                        1816  1659            8β,15-dimethyl-9α,β,15-                                       dihydroxy-13-trans-                                                           prostenoic acid                                         1817  1659            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          prostenoic acid                                         1818  1660            8α,15-dimethyl-9α,15-                                             dihydroxy-8-iso-13-                                                           trans-prostenoic acid                                   1819  1660            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-13-                                                          trans-prostenoic acid                                   1820  1730            8β,15-dimethyl-9α/β,15-                                       dihydroxy-13-trans,17-                                                        cis-prostadienoic acid                                  1821  1730            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          17-cis-prostadienoic                                                          acid                                                    1822  1731            8α,15-dimethyl-9α/β,15-                                      dihydroxy-8-iso-13-                                                           trans,17-cis-prosta-                                                          dienoic acid                                            1823  1731            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            1824  1738            8β,15-dimethyl-9α/β,                                          15-dihydroxy-7a,7b-                                                           bishomo-13-trans-                                                             prostenoic acid                                         1825  1738            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-13-trans-prost-                                                          enoic acid                                              1826  1746            8β,15-dimethyl-9α/β,                                          15-dihydroxy-3-oxa-16,                                                        16-dimethyl-13-trans-                                                         prostenoic acid                                         ______________________________________                                        Ex-   Starting 9α/β, (or                                           ample 9α),15-dihydroxy-                                                                       Product                                                       or 9α/β (or 9α),                                                             8,15-dimethyl-15-hy-                                          11α,15-dihydroxy                                                                        droxy-prostenoic                                              derivative of   acids                                                         Example                                                                 ______________________________________                                        1827  1746            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-16,                                                          16-dimethyl-13-trans-                                                         prostenoic acid                                         1828  1750            8β,15-dimethyl-9α/β,                                          15-dihydroxy-3-oxa-                                                           13-trans,17-cis-                                                              prostadienoic acid                                      1829  1750            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            1830  1770            8β,15-dimethyl-9α/β,                                          15-dihydroxy-5-cis,                                                           13-trans,17-cis-prosta-                                                       trienoic acid                                           1831  1770            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                           1832  1778            8β,15-dimethyl-9α/β,                                          15-dihydroxy-20-ethyl-                                                        5-cis,13-trans-                                                               prostadienoic acid                                      1833  1778            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-5-                                                        cis,13-trans-prosta-                                                          dienoic acid                                            1834  1523            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans-prostenoic acid                                   1835  1523            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans-prostenoic acid                                   1836  1524            8α,15-dimethyl-9α/β,                                         11α,15-trihydroxy-8-                                                    iso-13-trans-pros-                                                            tenoic acid                                             1837  1524            8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-                                                       8-iso-13-trans-                                                               prostenoic acid                                         1838  1535            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans,17-cis-prosta-                                                          dienoic acid                                            1839  1535            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans,17-cis-prosta-                                                          dienoic acid                                            1840  1539            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-20-                                                   ethyl-13-trans-pro-                                                           stenoic acid                                            1841  1539            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-20-                                                    ethyl-13-trans-pro-                                                           stenoic acid                                            1842  1551            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-7a,                                                   7b-bishomo-13-trans-                                                          prostenoic acid                                         1843  1551            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-7a,                                                    7b-bishomo-13-trans-                                                          prostenoic acid                                         1844  1555            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-2-                                                    ethyl-13-trans-                                                               prostenoic acid                                         1845  1555            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-2-                                                     ethyl-13-trans-                                                               prostenoic acid                                         1846  1559            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3,3,                                                  20-trimethyl-13-trans-                                                        prostenoic acid                                         1847  1559            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3,3,                                                   20-trimethyl-13-trans-                                                        prostenoic acid                                         1848  1563            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans-prostenoic                                                       acid                                                    1849  1563            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-13-trans-prostenoic                                                       acid                                                    1850  1571            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans,17-cis-                                                          prostadienoic acid                                      1851  1571            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-oxa-                                                 13-trans,17-cis-prosta-                                                       dienoic acid                                            1852  1599            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-5-                                                    cis,13-trans-prosta-                                                          dienoic acid                                            1853  1599            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-5-                                                     cis,13-trans-prosta-                                                          dienoic acid                                            1854  1603            8β,15-dimethyl-9α/β,                                          11α ,15-trihydroxy-5-cis,                                               13-trans,17-cis-prosta-                                                       trienoic acid                                           1855  1603            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-5-                                                     cis,13-trans,17-cis-                                                          prostatrienoic acid                                     1856  1611            8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-4-nor-                                                20-methyl-5-cis,13-                                                           trans-prostadienoic                                                           acid                                                    1857  1611            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4-                                                     nor-20-methyl-5-cis,                                                          13-trans-prostadienoic                                                        acid                                                    1858  1623            8β,15-dimethyl-9α/β ,                                         11α,15-trihydroxy-4a,                                                   4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                           1859  1623            8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4a,                                                    4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                           ______________________________________                                    

EXAMPLES 1860-1876

Treatment of the 8,15-dimethyl-9-oxo-11α-hydroxy derivatives listed inTable 46 below with aqueous acetic acid by the procedure described inExample 1387 is productive of the corresponding 10-prostenoic acidproducts of the table.

                  TABLE 46                                                        ______________________________________                                        Ex-   Starting 8,15-di-                                                       ample methyl-9-oxo-11α-                                                                       Product                                                       hydroxy deriva- 8,15-dimethyl-9-oxo-                                          tives of Example                                                                              10-prostenoic acid                                      ______________________________________                                        1860  1835            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans-                                                       prostadienoic acid                                      1861  1837            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10,                                                          13-trans-prostadienoic                                                        acid                                                    1862  1839            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans,                                                       17-cis-prostatrienoic                                                         acid                                                    1863  1841            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-                                                          10,13-trans-prosta-                                                           dienoic acid                                            1864  1843            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-10,13-trans-                                                             prostadienoic acid                                      1865  1845            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-2-ethyl-10,13-                                                        trans-prostadienoic                                                           acid                                                    1866  1847            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3,3,20-tri-                                                        methyl-10,13-trans-                                                           prostadienoic acid                                      1867  1849            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,13-                                                       trans-prostadienoic                                                           acid                                                    1868  1851            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                           1869  1853            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,13-                                                       trans-prostatrienoic                                                          acid                                                    1870  1855            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,                                                          13-trans,17-cis-prosta-                                                       tetraenoic acid                                         1871  1857            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4-nor-20-                                                          methyl-5-cis,10,13-                                                           trans-prostatrienoic                                                          acid                                                    1872  1859            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4a,4b-bis-                                                         homo-5-cis,10,13-trans,                                                       17-cis-prostatetraenoic                                                       acid                                                    1873  1812            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-10-prostenoic                                                         acid                                                    1874  1815            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-3-oxa-10-                                                             prostenoic acid                                         1875  1814            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-7a,7b-bishomo-                                                        10-prostenoic acid                                      1876  1813            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10-                                                          prostenoic acid                                         ______________________________________                                    

EXAMPLE 1877 Preparation of 3-methoxy-1-octyne

To an ice-cooled solution of 63 g. of 1-octyn-3-ol in 300 ml. ofdimethoxyethane is added under an inert atmosphere 312 ml. of 1.6 Mn-butyllithium in hexane dropwise over 1 hour. To the mixture is thenadded 145 g. of methyl iodide and the resulting mixture is stirred atambient temperatures for 24 hours and then heated to 60°C. for 1 hour.The mixture is cooled and poured into cold dilute hydrochloric acid. Theorganic phase is separated, washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to an oil, dried (Na₂ SO₄), and evaporated toan oil. Fractional distillation of the oil in vacuo yields the productas a colorless oil.

EXAMPLE 1878 Preparation of 1-Iodo-3-methoxy-trans-1-octene

Treatment of 3-methoxy-1-octyne (Example 1877) with disiamylborane,trimethylamine oxide, sodium hydroxide and iodine by the proceduredescribed in Example 996 furnishes the title product.

EXAMPLE 1879 Preparation of 3-Methoxy-trans-1-octenyl lithium

Treatment of 1-iodo-3-methoxy-trans-1-octene (Example 1878) with butyllithium in the manner or Example 961 pro provides a toluene-hexanesolution of the subject trans-vinyl lithium derivative.

EXAMPLE 1880 Preparation of Lithium(3-methoxy-trans-1-octenyl)trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 963 from a hydrocarbon solution of3-methoxy-trans-1-octenyl lithium (Example 1879)and trimethylaluminum.

EXAMPLES 1881-1895

Treatment of the cycloalkenones listed in Table 47 with lithium(3-methoxy-trans-1-octenyl)trimethylalanate (Example 1880 ) by theprocedure described in Example 957 with the omission of the 80% aqueousacetic acid treatment (80°C., 1 hour) followed by saponfication of theintermediate alkyl prostenoates by the procedure described in Example122 furnishes the product 9-oxo-15-methoxy-13-trans-prostenoic acids ofthe table.

                  TABLE 47                                                        ______________________________________                                        Ex-     Starting cyclo-                                                                            Product 9-oxo-15-                                        ample   alkenone of  methoxy-13-trans-                                                Example      prostenoic acid                                          ______________________________________                                        1881    23           9-oxo-7a,7b-bishomo-                                                          15-methoxy-13-trans-                                                          prostenoic acid                                          1882    31           9-oxo-2-ethyl-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                             1883    41           9-oxo-3,3-dimethyl-                                                           15-methoxy-13-trans-                                                          prostenoic acid                                          1884    46           9-oxo-3-oxa-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                     1885    53           9-oxo-7-nor-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                     1886    70           9-oxo-2-fluoro-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                          1887    74           9-oxo-7a-homo-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                             1888    79           9-oxo-2-phenyl-15-                                                            methoxy-13-trans-pro-                                                         stenoic acid                                             1889    99           9-oxo-2-methyl-15-                                                            methoxy-13-trans-pro-                                                         stenoic acid                                             1890    111          9-oxo-10a-homo-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                          1891    118          9-oxo-3-thia-15-                                                              methoxy-13-trans-                                                             prostenoic acid                                          1892    900          9-oxo-15-methoxy-5-                                                           cis,13-trans-pro-                                                             stadienoic acid                                          1893    1144         9-oxo-4-nor-15-methoxy-                                                       13-trans-prostadienoic                                                        acid-1894 1145  9-oxo-4-homo-15-                                              methoxy-5-cis,13-                                                             trans-prostadienoic                                                           acid                                                     1895    1146         9-oxo-4a,4b-bishomo-                                                          15-methoxy-13-trans-                                                          prostadienoic acid                                       ______________________________________                                    

EXAMPLES 1896-1910

Treatment of the 9-oxo-15-methoxy-13-trans-prostenoic acids listed inTable 48 below with lithium perhydro-9b-boraphenalylhydride by theprocedure described in Example 737 furnishes the9α-hydroxy-15-methoxy-13-trans-prostenoic acids of the Table.

                  TABLE 48                                                        ______________________________________                                               Starting 9-oxo-                                                        Ex-    15-methoxy-13-                                                                              Product 9α-hydroxy-15-                             ample  trans-prosten-                                                                              methoxy-13-trans-                                               oic acid of   prostenoic acid                                                 Example                                                                ______________________________________                                        1896   1881          9α-hydroxy-7a,7b-bis-                                                   homo-15-methoxy-13-                                                           trans-prostenoic acid                                    1897   1882          9α-hydroxy-2-ethyl-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                          1898   1883          9α-hydroxy-3,3-dimethyl-                                                15-methoxy-13-trans-                                                          prostenoic acid                                          1899   1884          9α-hydroxy-3-oxa-15-                                                    methoxy-13-trans-                                                             prostenoic acid                                          1900   1885          9α-hydroxy-7-nor-15-                                                    methoxy-13-trans-pro                                                          prostenoic acid                                          1901   1886          9α-hydroxy-2-fluoro-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1902   1887          9α-hydroxy-7a-homo-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                          1903   1888          9α-hydroxy-2-phenyl-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1904   1889          9α-hydroxy-2-methyl-                                                    methoxy-13-trans-                                                             prostenoic acid                                          1905   1890          9α-hydroxy-10a-homo-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                          1906   1891          9α-hydroxy-3-thia-15-                                                   methoxy-13-trans-                                                             prostenoic acid                                          1907   1892          9α-hydroxy-15-methoxy-                                                  5-cis,13-trans-prosta-                                                        dienoic acid                                             1908   1893          9α-hydroxy-4-nor-15-                                                    methoxy-5-cis,13-                                                             trans-prostadienoic                                                           acid                                                     1909   1894          9α-hydroxy-4-homo-15-                                                   methoxy-5-cis,13-trans-                                                       prostadienoic acid                                       1910    1895β   9α-hydroxy-4a,4b-bis-                                                   homo-15-methoxy-13-                                                           trans-prostenoic acid                                    ______________________________________                                    

EXAMPLE 1911 Preparation of2-(6-carboxy-2-cis-hexenyl)3,4-oxidocyclopentanol

A solution of 5.0 g. (35 mmoles) of5-hydroxy-2,3-oxidocyclopentylacetaldehyde- γ-lactol (isomeric mixture;E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 25 ml. ofDMSO is added during 0.5 minutes at 20°C. to a stirred solution of theWithig reagent [E. J. Corey et al., JACS, 91 5675 (1969); also Example1108] and dimsyl sodium prepared from 23.5 g. (53 mmoles) of4-carboxybutyltriphenylphosphonium bromide, 6.1 g. (140 mmoles) of 57%sodium hydride dispersion, and 230 ml. of DMSO (dimethylsulfoxide).

The solution is stirred at ambient temperatures for 2 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The reaction mixture is worked up as described in Example 1105,and the crude product is purified by dry column chromatography on silicagel to provide the title compound (mixture of two stereoisomers) as anoil, IR (film) 3450, 1710, and 832 cm⁻ ¹.

EXAMPLE 1912 Preparation of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

A stirred solution of 2.98 g. (13.2 mmoles) of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example 1911) in 66ml. of acetone is treated dropwise with 3.30 ml. of 8N chromic acid in8N M₂ SO₄ during 20 minutes at -10° to -5°C. The solution is stirred at-5°C. for 10 minutes and treated successively with a few drops ofisopropanol and 12 ml. of water. The mixture is filtered, and thefiltrate is concentrated saturated with sodium chloride, and extractedwith ethyl acetate. The extract is washed with brine, dried over MgSO₄,and evaporated to give an oil, IR (film) 1740, 1710, and 840 cm⁻ ¹.

EXAMPLE 1913 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of (pH or 10.2-10.5) of 2.42 g. (10.8 mmoles) of2-(6-carboxy-2-cis-hexenyl)3,4-oxidocyclopentanone (Example 1912) 4.58g. (43.2 mmoles) of sodium carbonate, and 216 ml. of water is allowed tostand at room temperatures under nitrogen for 24 hours. The solution isacidified at 15°C. with hydrochloric acid and extracted with ethylacetate. The extract is washed with brine, dried over MgSO₄, andevaporated to give an oil; IR (film) 1700 (carbonyl groups) and 1630 cm⁻¹ (conjugated olefin); NMR 7.11 (1), 5.54 (2), and 4.95 (1)δ.

We claim
 1. Compounds of the formula: ##SPC19##wherein p is an integerfrom 2 to 6, inclusive, and Y is a divalent radical of the formulae##EQU21##
 2. The compound according to claim 1 wherein p is 3 and Y is##EQU22## 2-(carboxy-2-cis-hexenyl)-3,4-epoxycyclopentan-1-one.
 3. Thecompound according to claim 1 wherein p is 3 and Y is ##EQU23##2-(6-carboxy-2-cis-hexenyl)-3,4-epoxycyclopentan-1-ol.